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Insufficient sleep impairs women’s insulin sensitivity
Women, particularly those who are postmenopausal, who sleep less than the recommended 7 hours per night may have impaired insulin sensitivity regardless of their degree of adiposity, a randomized crossover trial reveals.
The research was published recently in Diabetes Care.
Nearly 40 women were randomly assigned to either restricted sleep or adequate sleep for 6 weeks, then crossed over to the other sleep condition. During sleep restriction, women slept an average of 6.2 hours per night versus 7-9 hours per night.
Both fasting insulin levels and insulin resistance were significantly increased during sleep restriction, with the effect on insulin resistance particularly notable in postmenopausal women. This was independent of adiposity and changes in adiposity.
“What we’re seeing is that more insulin is needed to normalize glucose levels in the women under conditions of sleep restriction,” said senior author Marie-Pierre St-Onge, PhD, director of the Center of Excellence for Sleep and Circadian Research at Columbia University Vagelos College of Physicians and Surgeons, New York, in a release.
“Even then, the insulin may not have been doing enough to counteract rising blood glucose levels of postmenopausal women,” she stated.
Prolonged lack of sleep may accelerate diabetes progression
Dr. St-Onge added,
Dr. St-Onge said in an interview that it was crucial to show the impact of sleep restriction in a randomized study, because “observational studies don’t provide information on causality.”
The study did not rely on people “living in our clinical research facility,” but instead enrolled individuals who were “living their lives,” and the reduction in sleep achieved was “similar to what is seen in the general population with sleep,” she said.
Dr. St-Onge therefore believes the findings indicate that sleep has been overlooked as a contributory factor in insulin sensitivity.
Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, said in an interview that this is an “important study [that] builds on what we have seen on the importance of sleep for metabolic outcomes and diabetes.”
He continued, “There have been several studies showing the association of sleep and diabetes, but that does not necessarily mean cause and effect.”
On the other hand, Dr. Gabbay said, “randomizing people can help see sleep influences on key metabolic measures of diabetes, [which] helps to build a stronger case that sleep disturbances can cause worsening metabolic health.”
He emphasized that both the quantity and quality of sleep are “critical for optimal diabetes health” and highlighted that the ADA’s Standards of Care “recommends screening for sleep issues and counseling to improve sleep.”
“This study provides new insight into the health effects of even small sleep deficits in women across all stages of adulthood and racial and ethnic backgrounds,” commented Corinne Silva, PhD, program director in the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, which co-funded the study.
The authors note that more than one-third of adults sleep less than the recommended 7 hours per night, which is “concerning given robust associations of short sleep with cardiometabolic diseases.”
Moreover, “women report poorer sleep than men,” explained Marishka Brown, PhD, director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute, which also co-funded the study.
“So understanding how sleep disturbances impact their health across the lifespan is critical, especially for postmenopausal women,” she said, particularly because previous studies have not reflected real-world sleep patterns or have focused on men.
The researchers conducted a trial to evaluate the causal impact of prolonged, mild sleep restriction on cardiometabolic risk factors in women as part of the American Heart Association Go Red for Women Strategically Focused Research Network.
They recruited metabolically healthy women aged 20-75 years who were at increased risk for cardiometabolic disease due to having either overweight or class I obesity or at least one parent with type 2 diabetes, hyperlipidemia, or cardiovascular disease.
They were also required to have a habitual total sleep time on actigraphy of 7-9 hours per night and low risk for sleep apnea. Exclusion criteria included excessive caffeine intake, a significantly advanced or delayed sleep phase, shift work, and travel across time zones.
The participants were randomly assigned to either adequate sleep, defined as 7-9 hours per night, or sleep restriction, defined as a reduction in sleep duration of 1.5 hours per night, for 6 weeks. They were then crossed over to the other sleep condition.
Assessments, including MRI and oral glucose tolerance tests, were performed at baseline and at the end of each study phase.
The researchers report on 38 women who took part in the trial, of whom 11 were postmenopausal. The mean age was 37.6 years; 31.6% self-identified as Black and 26.3% as Hispanic. The mean body mass index (BMI) was 25.5.
Postmenopausal women had a higher mean age than other women, at 56.1 years versus 30.1 years, and a higher baseline fasting blood glucose, at 5.26 mmol/L (94.68 mg/dL) versus 4.70 mmol/L (84.6 mg/dL).
The team reported that compliance with the sleep protocol was “excellent,” with women during sleep restriction having a reduction in total sleep time of 1.34 hours per night versus women in the adequate sleep arm (P < .0001).
Sleep restriction was also associated with significant increases in fasting plasma insulin versus adequate sleep, at a beta value of 0.68 pmol/L (P = .016), and significantly increased Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values (beta = 0.30; P = .016).
The impact on HOMA-IR values was significantly more pronounced in postmenopausal than menopausal women, at beta values of 0.45 versus 0.27 (P for interaction = .042).
Sleep restriction had no significant effect on fasting plasma glucose levels, and the association between sleep duration and cardiometabolic parameters was not modified by the proportion of either total or visceral adipose tissue, or by changes in adiposity.
This clinical trial was supported by the American Heart Association, a National Institutes of Health Clinical and Translational Science Award to Columbia University, and N.Y. Nutrition Obesity Research Center. Individual authors received support from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
Women, particularly those who are postmenopausal, who sleep less than the recommended 7 hours per night may have impaired insulin sensitivity regardless of their degree of adiposity, a randomized crossover trial reveals.
The research was published recently in Diabetes Care.
Nearly 40 women were randomly assigned to either restricted sleep or adequate sleep for 6 weeks, then crossed over to the other sleep condition. During sleep restriction, women slept an average of 6.2 hours per night versus 7-9 hours per night.
Both fasting insulin levels and insulin resistance were significantly increased during sleep restriction, with the effect on insulin resistance particularly notable in postmenopausal women. This was independent of adiposity and changes in adiposity.
“What we’re seeing is that more insulin is needed to normalize glucose levels in the women under conditions of sleep restriction,” said senior author Marie-Pierre St-Onge, PhD, director of the Center of Excellence for Sleep and Circadian Research at Columbia University Vagelos College of Physicians and Surgeons, New York, in a release.
“Even then, the insulin may not have been doing enough to counteract rising blood glucose levels of postmenopausal women,” she stated.
Prolonged lack of sleep may accelerate diabetes progression
Dr. St-Onge added,
Dr. St-Onge said in an interview that it was crucial to show the impact of sleep restriction in a randomized study, because “observational studies don’t provide information on causality.”
The study did not rely on people “living in our clinical research facility,” but instead enrolled individuals who were “living their lives,” and the reduction in sleep achieved was “similar to what is seen in the general population with sleep,” she said.
Dr. St-Onge therefore believes the findings indicate that sleep has been overlooked as a contributory factor in insulin sensitivity.
Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, said in an interview that this is an “important study [that] builds on what we have seen on the importance of sleep for metabolic outcomes and diabetes.”
He continued, “There have been several studies showing the association of sleep and diabetes, but that does not necessarily mean cause and effect.”
On the other hand, Dr. Gabbay said, “randomizing people can help see sleep influences on key metabolic measures of diabetes, [which] helps to build a stronger case that sleep disturbances can cause worsening metabolic health.”
He emphasized that both the quantity and quality of sleep are “critical for optimal diabetes health” and highlighted that the ADA’s Standards of Care “recommends screening for sleep issues and counseling to improve sleep.”
“This study provides new insight into the health effects of even small sleep deficits in women across all stages of adulthood and racial and ethnic backgrounds,” commented Corinne Silva, PhD, program director in the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, which co-funded the study.
The authors note that more than one-third of adults sleep less than the recommended 7 hours per night, which is “concerning given robust associations of short sleep with cardiometabolic diseases.”
Moreover, “women report poorer sleep than men,” explained Marishka Brown, PhD, director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute, which also co-funded the study.
“So understanding how sleep disturbances impact their health across the lifespan is critical, especially for postmenopausal women,” she said, particularly because previous studies have not reflected real-world sleep patterns or have focused on men.
The researchers conducted a trial to evaluate the causal impact of prolonged, mild sleep restriction on cardiometabolic risk factors in women as part of the American Heart Association Go Red for Women Strategically Focused Research Network.
They recruited metabolically healthy women aged 20-75 years who were at increased risk for cardiometabolic disease due to having either overweight or class I obesity or at least one parent with type 2 diabetes, hyperlipidemia, or cardiovascular disease.
They were also required to have a habitual total sleep time on actigraphy of 7-9 hours per night and low risk for sleep apnea. Exclusion criteria included excessive caffeine intake, a significantly advanced or delayed sleep phase, shift work, and travel across time zones.
The participants were randomly assigned to either adequate sleep, defined as 7-9 hours per night, or sleep restriction, defined as a reduction in sleep duration of 1.5 hours per night, for 6 weeks. They were then crossed over to the other sleep condition.
Assessments, including MRI and oral glucose tolerance tests, were performed at baseline and at the end of each study phase.
The researchers report on 38 women who took part in the trial, of whom 11 were postmenopausal. The mean age was 37.6 years; 31.6% self-identified as Black and 26.3% as Hispanic. The mean body mass index (BMI) was 25.5.
Postmenopausal women had a higher mean age than other women, at 56.1 years versus 30.1 years, and a higher baseline fasting blood glucose, at 5.26 mmol/L (94.68 mg/dL) versus 4.70 mmol/L (84.6 mg/dL).
The team reported that compliance with the sleep protocol was “excellent,” with women during sleep restriction having a reduction in total sleep time of 1.34 hours per night versus women in the adequate sleep arm (P < .0001).
Sleep restriction was also associated with significant increases in fasting plasma insulin versus adequate sleep, at a beta value of 0.68 pmol/L (P = .016), and significantly increased Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values (beta = 0.30; P = .016).
The impact on HOMA-IR values was significantly more pronounced in postmenopausal than menopausal women, at beta values of 0.45 versus 0.27 (P for interaction = .042).
Sleep restriction had no significant effect on fasting plasma glucose levels, and the association between sleep duration and cardiometabolic parameters was not modified by the proportion of either total or visceral adipose tissue, or by changes in adiposity.
This clinical trial was supported by the American Heart Association, a National Institutes of Health Clinical and Translational Science Award to Columbia University, and N.Y. Nutrition Obesity Research Center. Individual authors received support from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
Women, particularly those who are postmenopausal, who sleep less than the recommended 7 hours per night may have impaired insulin sensitivity regardless of their degree of adiposity, a randomized crossover trial reveals.
The research was published recently in Diabetes Care.
Nearly 40 women were randomly assigned to either restricted sleep or adequate sleep for 6 weeks, then crossed over to the other sleep condition. During sleep restriction, women slept an average of 6.2 hours per night versus 7-9 hours per night.
Both fasting insulin levels and insulin resistance were significantly increased during sleep restriction, with the effect on insulin resistance particularly notable in postmenopausal women. This was independent of adiposity and changes in adiposity.
“What we’re seeing is that more insulin is needed to normalize glucose levels in the women under conditions of sleep restriction,” said senior author Marie-Pierre St-Onge, PhD, director of the Center of Excellence for Sleep and Circadian Research at Columbia University Vagelos College of Physicians and Surgeons, New York, in a release.
“Even then, the insulin may not have been doing enough to counteract rising blood glucose levels of postmenopausal women,” she stated.
Prolonged lack of sleep may accelerate diabetes progression
Dr. St-Onge added,
Dr. St-Onge said in an interview that it was crucial to show the impact of sleep restriction in a randomized study, because “observational studies don’t provide information on causality.”
The study did not rely on people “living in our clinical research facility,” but instead enrolled individuals who were “living their lives,” and the reduction in sleep achieved was “similar to what is seen in the general population with sleep,” she said.
Dr. St-Onge therefore believes the findings indicate that sleep has been overlooked as a contributory factor in insulin sensitivity.
Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, said in an interview that this is an “important study [that] builds on what we have seen on the importance of sleep for metabolic outcomes and diabetes.”
He continued, “There have been several studies showing the association of sleep and diabetes, but that does not necessarily mean cause and effect.”
On the other hand, Dr. Gabbay said, “randomizing people can help see sleep influences on key metabolic measures of diabetes, [which] helps to build a stronger case that sleep disturbances can cause worsening metabolic health.”
He emphasized that both the quantity and quality of sleep are “critical for optimal diabetes health” and highlighted that the ADA’s Standards of Care “recommends screening for sleep issues and counseling to improve sleep.”
“This study provides new insight into the health effects of even small sleep deficits in women across all stages of adulthood and racial and ethnic backgrounds,” commented Corinne Silva, PhD, program director in the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, which co-funded the study.
The authors note that more than one-third of adults sleep less than the recommended 7 hours per night, which is “concerning given robust associations of short sleep with cardiometabolic diseases.”
Moreover, “women report poorer sleep than men,” explained Marishka Brown, PhD, director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute, which also co-funded the study.
“So understanding how sleep disturbances impact their health across the lifespan is critical, especially for postmenopausal women,” she said, particularly because previous studies have not reflected real-world sleep patterns or have focused on men.
The researchers conducted a trial to evaluate the causal impact of prolonged, mild sleep restriction on cardiometabolic risk factors in women as part of the American Heart Association Go Red for Women Strategically Focused Research Network.
They recruited metabolically healthy women aged 20-75 years who were at increased risk for cardiometabolic disease due to having either overweight or class I obesity or at least one parent with type 2 diabetes, hyperlipidemia, or cardiovascular disease.
They were also required to have a habitual total sleep time on actigraphy of 7-9 hours per night and low risk for sleep apnea. Exclusion criteria included excessive caffeine intake, a significantly advanced or delayed sleep phase, shift work, and travel across time zones.
The participants were randomly assigned to either adequate sleep, defined as 7-9 hours per night, or sleep restriction, defined as a reduction in sleep duration of 1.5 hours per night, for 6 weeks. They were then crossed over to the other sleep condition.
Assessments, including MRI and oral glucose tolerance tests, were performed at baseline and at the end of each study phase.
The researchers report on 38 women who took part in the trial, of whom 11 were postmenopausal. The mean age was 37.6 years; 31.6% self-identified as Black and 26.3% as Hispanic. The mean body mass index (BMI) was 25.5.
Postmenopausal women had a higher mean age than other women, at 56.1 years versus 30.1 years, and a higher baseline fasting blood glucose, at 5.26 mmol/L (94.68 mg/dL) versus 4.70 mmol/L (84.6 mg/dL).
The team reported that compliance with the sleep protocol was “excellent,” with women during sleep restriction having a reduction in total sleep time of 1.34 hours per night versus women in the adequate sleep arm (P < .0001).
Sleep restriction was also associated with significant increases in fasting plasma insulin versus adequate sleep, at a beta value of 0.68 pmol/L (P = .016), and significantly increased Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values (beta = 0.30; P = .016).
The impact on HOMA-IR values was significantly more pronounced in postmenopausal than menopausal women, at beta values of 0.45 versus 0.27 (P for interaction = .042).
Sleep restriction had no significant effect on fasting plasma glucose levels, and the association between sleep duration and cardiometabolic parameters was not modified by the proportion of either total or visceral adipose tissue, or by changes in adiposity.
This clinical trial was supported by the American Heart Association, a National Institutes of Health Clinical and Translational Science Award to Columbia University, and N.Y. Nutrition Obesity Research Center. Individual authors received support from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. No relevant financial relationships were declared.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>“If that’s sustained over time, it is possible that prolonged insufficient sleep among individuals with prediabetes could accelerate the progression to type 2 d</metaDescription> <articlePDF/> <teaserImage>287203</teaserImage> <teaser>“What we’re seeing is that more insulin is needed to normalize glucose levels in the women under conditions of sleep restriction.” </teaser> <title>Insufficient sleep impairs women’s insulin sensitivity</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>icymit2d</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>15</term> <term>21</term> <term>71871</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> <term>86</term> </sections> <topics> <term canonical="true">205</term> <term>247</term> <term>296</term> <term>322</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24010e3a.jpg</altRep> <description role="drol:caption">Dr. Robert A. Gabbay</description> <description role="drol:credit">Joslin Diabetes Center</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Insufficient sleep impairs women’s insulin sensitivity</title> <deck/> </itemMeta> <itemContent> <p>Women, particularly those who are postmenopausal, who sleep less than the recommended 7 hours per night may have impaired insulin sensitivity regardless of their degree of adiposity, a randomized <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT02835261">crossover trial</a></span> reveals.</p> <p>The research was <span class="Hyperlink"><a href="https://diabetesjournals.org/care/article-abstract/doi/10.2337/dc23-1156/153802/Chronic-Insufficient-Sleep-in-Women-Impairs">published recently</a></span> in Diabetes Care.<br/><br/>Nearly 40 women were randomly assigned to either restricted sleep or adequate sleep for 6 weeks, then crossed over to the other sleep condition. During sleep restriction, women slept an average of 6.2 hours per night versus 7-9 hours per night.<br/><br/>Both fasting insulin levels and insulin resistance were significantly increased during sleep restriction, with the effect on insulin resistance particularly notable in postmenopausal women. This was independent of adiposity and changes in adiposity.<br/><br/>“What we’re seeing is that more insulin is needed to normalize glucose levels in the women under conditions of sleep restriction,” said senior author Marie-Pierre St-Onge, PhD, director of the Center of Excellence for Sleep and Circadian Research at Columbia University Vagelos College of Physicians and Surgeons, New York, in a release.<br/><br/>“Even then, the insulin may not have been doing enough to counteract rising blood glucose levels of postmenopausal women,” she stated.<br/><br/></p> <h2>Prolonged lack of sleep may accelerate diabetes progression</h2> <p>Dr. St-Onge added, <span class="tag metaDescription">“If that’s sustained over time, it is possible that prolonged insufficient sleep among individuals with prediabetes could accelerate the progression to type 2 diabetes.”</span></p> <p>Dr. St-Onge said in an interview that it was crucial to show the impact of sleep restriction in a randomized study, because “observational studies don’t provide information on causality.”<br/><br/>The study did not rely on people “living in our clinical research facility,” but instead enrolled individuals who were “living their lives,” and the reduction in sleep achieved was “similar to what is seen in the general population with sleep,” she said.<br/><br/>Dr. St-Onge therefore believes the findings indicate that sleep has been overlooked as a contributory factor in insulin sensitivity.<br/><br/>Robert Gabbay, MD, PhD, chief scientific and medical officer at the American Diabetes Association, said in an interview that this is an “important study [that] builds on what we have seen on the importance of sleep for metabolic outcomes and diabetes.”[[{"fid":"287203","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Robert A. Gabbay, MD, PhD, FACP, chief medical officer at Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School, in Boston","field_file_image_credit[und][0][value]":"Joslin Diabetes Center","field_file_image_caption[und][0][value]":"Dr. Robert A. Gabbay"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>He continued, “There have been several studies showing the association of sleep and diabetes, but that does not necessarily mean cause and effect.”<br/><br/>On the other hand, Dr. Gabbay said, “randomizing people can help see sleep influences on key metabolic measures of diabetes, [which] helps to build a stronger case that sleep disturbances can cause worsening metabolic health.”<br/><br/>He emphasized that both the quantity and quality of sleep are “critical for optimal diabetes health” and highlighted that the ADA’s <span class="Hyperlink"><a href="https://diabetesjournals.org/clinical/article/41/1/4/148029/Standards-of-Care-in-Diabetes-2023-Abridged-for">Standards of Care</a></span> “recommends screening for sleep issues and counseling to improve sleep.”<br/><br/>“This study provides new insight into the health effects of even small sleep deficits in women across all stages of adulthood and racial and ethnic backgrounds,” commented Corinne Silva, PhD, program director in the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases, which co-funded the study.<br/><br/>The authors note that more than one-third of adults sleep less than the recommended 7 hours per night, which is “concerning given robust associations of short sleep with cardiometabolic diseases.”<br/><br/>Moreover, “women report poorer sleep than men,” explained Marishka Brown, PhD, director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute, which also co-funded the study.<br/><br/>“So understanding how sleep disturbances impact their health across the lifespan is critical, especially for postmenopausal women,” she said, particularly because previous studies have not reflected real-world sleep patterns or have focused on men.<br/><br/>The researchers conducted a trial to evaluate the causal impact of prolonged, mild sleep restriction on cardiometabolic risk factors in women as part of the American Heart Association <span class="Hyperlink"><a href="https://www.goredforwomen.org/">Go Red for Women</a></span> Strategically Focused Research Network.<br/><br/>They recruited metabolically healthy women aged 20-75 years who were at increased risk for cardiometabolic disease due to having either overweight or class I obesity or at least one parent with type 2 diabetes, hyperlipidemia, or cardiovascular disease.<br/><br/>They were also required to have a habitual total sleep time on actigraphy of 7-9 hours per night and low risk for sleep apnea. Exclusion criteria included excessive caffeine intake, a significantly advanced or delayed sleep phase, shift work, and travel across time zones.<br/><br/>The participants were randomly assigned to either adequate sleep, defined as 7-9 hours per night, or sleep restriction, defined as a reduction in sleep duration of 1.5 hours per night, for 6 weeks. They were then crossed over to the other sleep condition.<br/><br/>Assessments, including MRI and oral glucose tolerance tests, were performed at baseline and at the end of each study phase.<br/><br/>The researchers report on 38 women who took part in the trial, of whom 11 were postmenopausal. The mean age was 37.6 years; 31.6% self-identified as Black and 26.3% as Hispanic. The mean body mass index (BMI) was 25.5.<br/><br/>Postmenopausal women had a higher mean age than other women, at 56.1 years versus 30.1 years, and a higher baseline fasting blood glucose, at 5.26 mmol/L (94.68 mg/dL) versus 4.70 mmol/L (84.6 mg/dL).<br/><br/>The team reported that compliance with the sleep protocol was “excellent,” with women during sleep restriction having a reduction in total sleep time of 1.34 hours per night versus women in the adequate sleep arm (<em>P</em> < .0001).<br/><br/>Sleep restriction was also associated with significant increases in fasting plasma insulin versus adequate sleep, at a beta value of 0.68 pmol/L (<em>P</em> = .016), and significantly increased Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values (beta = 0.30; <em>P </em>= .016).<br/><br/>The impact on HOMA-IR values was significantly more pronounced in postmenopausal than menopausal women, at beta values of 0.45 versus 0.27 (<em>P</em> for interaction = .042).<br/><br/>Sleep restriction had no significant effect on fasting plasma glucose levels, and the association between sleep duration and cardiometabolic parameters was not modified by the proportion of either total or visceral adipose tissue, or by changes in adiposity.<br/><br/>This clinical trial was supported by the American Heart Association, a National Institutes of Health Clinical and Translational Science Award to Columbia University, and N.Y. Nutrition Obesity Research Center. Individual authors received support from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. No relevant financial relationships were declared.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/insufficient-sleep-impairs-womens-insulin-sensitivity-2023a1000tlz">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM DIABETES CARE
Does laughter offer better blood glucose control?
David S. Greene, PhD, associate professor in the department of rehabilitation and human services at the University of Northern Colorado, Greeley, has pioneered research into the field, one previously overlooked when it comes to diabetes management.
This news organization caught up with Dr. Greene to ask about his research along with the implications for diabetes care and for patient well-being.
Question: What prompted you to research the link between humor and diabetes control?
Answer: I was diagnosed with type 1 diabetes in 1966 and consequently have lived with, and studied, various aspects of diabetes for the past 57 years.
For a time, I maintained a small private practice counseling people with diabetes. There I noticed, anecdotally, that my clients’ ability to laugh at, and see the humor in, their diabetes correlated with their emotional adjustment to living with their condition.
While I could find research confirming the physical and psychological benefits of humor in general, I was unable to find any research specifically relating to humor and diabetes.
My new research agenda was born.
Q: What did your research reveal?
A: My first study, published in 2020, found that people living with diabetes displayed the same level of both types of positive, or affiliative and self-enhancing, humor as the norm group used in developing the Humor Styles Questionnaire.
This was a surprising finding given that individuals with diabetes are dealing with a life-altering, chronic illness, with higher rates of depression and anxiety. Moreover, positive humor scores are known to be negatively correlated with depression and anxiety.
While levels of aggressive humor were not altered in my study, people with diabetes did have higher levels of self-defeating humor in my study, which is correlated with psychiatric and somatic concerns, and symptomatology, and so is to be expected.
My second study, published in 2021, examined whether there was a difference between people with diabetes who had an hemoglobin A1c level of 6.99% or less versus those with levels of at least 7% on four disparate types of humor.
The A1c of 6.99% or less group scored significantly higher for both affiliative humor and self-enhancing humor. This implies that better diabetes control is associated with positive humor. This was expected, as was the finding that negative humor was not associated with better control.
On the other hand, there was no significant difference between participants on either type of negative humor, whether aggressive or self-defeating.
Finally, my third study, published in 2023 [with coauthor Nancy D. King, PhD], found that offering humor training to people with type 1 diabetes can strengthen both their affiliative and self-enhancing sense of humor, while leaving their aggressive or self-defeating humor unaffected.
Q: What is ‘positive humor,’ and why do you think it is associated with diabetes control?
A: Both affiliative and self-enhancing humor enhance a person’s sense of self and their relationships with others.
Affiliative humor has been shown to be positively correlated with self-esteem, psychological well-being, social intimacy, and emotional stability. It is also negatively correlated with depression and anxiety.
Self-enhancing humor involves the ability to maintain a humorous outlook on life and to use humor to regulate emotions and as a coping strategy. Like affiliative humor, it is correlated with cheerfulness, self-esteem, optimism, psychological well-being, and life satisfaction. It is negatively related to depression and anxiety.
The preponderance of literature suggests positive humor specifically is associated with buffering many of the risk factors and complications associated with diabetes.
Q: What could underlie the associations between humor and diabetes control?
A: Unfortunately, none of my studies have been able to determine cause and effect, although the most recent one came the closest.
While not reaching statistical significance, the mean reduction in A1c levels from 7.12% at baseline to 6.75% at the post–humor training assessment may very well imply a practical and psychological significance to patients.
I believe, with a larger sample size, significance will be achieved, and that the relationship between positive humor and diabetes control will be shown to be bidirectional, with positive humor improving diabetes control, and improved control improving positive humor.
I hypothesize this will also bring psychological and physiological benefits. After all, humor has already been associated with reduced blood glucose levels, reduced microvascular complications, improved heart health, reduced blood pressure, decreased levels of depression and anxiety.
Humor also helps us deal with stress and trauma, so a cause-and-effect relationship makes sense.
Q: Can a positive sense of humor be taught?
A: Absolutely. There is evidence that humor can be developed and strengthened. Paul McGhee, PhD, developed a seven-step humor training program that has been effective in elevating measures of humor across a number of studies.
Others have successfully developed their own protocols, and of course my third study demonstrated a significant increase in both affiliative and self-enhancing humor with training.
Q: Do you think humor training could be incorporated into diabetes care?
A: Humor training programs are easily accessible, incur low to no cost, and are easy to implement. Furthermore, once a person is trained, access to ongoing humor is free, readily available, and fun.
Several diabetes educators have also reported that humor can promote connections, encourage and support diabetes management, galvanize effectiveness, and increase an audience’s attention during education programs.
A version of this article appeared on Medscape.com.
David S. Greene, PhD, associate professor in the department of rehabilitation and human services at the University of Northern Colorado, Greeley, has pioneered research into the field, one previously overlooked when it comes to diabetes management.
This news organization caught up with Dr. Greene to ask about his research along with the implications for diabetes care and for patient well-being.
Question: What prompted you to research the link between humor and diabetes control?
Answer: I was diagnosed with type 1 diabetes in 1966 and consequently have lived with, and studied, various aspects of diabetes for the past 57 years.
For a time, I maintained a small private practice counseling people with diabetes. There I noticed, anecdotally, that my clients’ ability to laugh at, and see the humor in, their diabetes correlated with their emotional adjustment to living with their condition.
While I could find research confirming the physical and psychological benefits of humor in general, I was unable to find any research specifically relating to humor and diabetes.
My new research agenda was born.
Q: What did your research reveal?
A: My first study, published in 2020, found that people living with diabetes displayed the same level of both types of positive, or affiliative and self-enhancing, humor as the norm group used in developing the Humor Styles Questionnaire.
This was a surprising finding given that individuals with diabetes are dealing with a life-altering, chronic illness, with higher rates of depression and anxiety. Moreover, positive humor scores are known to be negatively correlated with depression and anxiety.
While levels of aggressive humor were not altered in my study, people with diabetes did have higher levels of self-defeating humor in my study, which is correlated with psychiatric and somatic concerns, and symptomatology, and so is to be expected.
My second study, published in 2021, examined whether there was a difference between people with diabetes who had an hemoglobin A1c level of 6.99% or less versus those with levels of at least 7% on four disparate types of humor.
The A1c of 6.99% or less group scored significantly higher for both affiliative humor and self-enhancing humor. This implies that better diabetes control is associated with positive humor. This was expected, as was the finding that negative humor was not associated with better control.
On the other hand, there was no significant difference between participants on either type of negative humor, whether aggressive or self-defeating.
Finally, my third study, published in 2023 [with coauthor Nancy D. King, PhD], found that offering humor training to people with type 1 diabetes can strengthen both their affiliative and self-enhancing sense of humor, while leaving their aggressive or self-defeating humor unaffected.
Q: What is ‘positive humor,’ and why do you think it is associated with diabetes control?
A: Both affiliative and self-enhancing humor enhance a person’s sense of self and their relationships with others.
Affiliative humor has been shown to be positively correlated with self-esteem, psychological well-being, social intimacy, and emotional stability. It is also negatively correlated with depression and anxiety.
Self-enhancing humor involves the ability to maintain a humorous outlook on life and to use humor to regulate emotions and as a coping strategy. Like affiliative humor, it is correlated with cheerfulness, self-esteem, optimism, psychological well-being, and life satisfaction. It is negatively related to depression and anxiety.
The preponderance of literature suggests positive humor specifically is associated with buffering many of the risk factors and complications associated with diabetes.
Q: What could underlie the associations between humor and diabetes control?
A: Unfortunately, none of my studies have been able to determine cause and effect, although the most recent one came the closest.
While not reaching statistical significance, the mean reduction in A1c levels from 7.12% at baseline to 6.75% at the post–humor training assessment may very well imply a practical and psychological significance to patients.
I believe, with a larger sample size, significance will be achieved, and that the relationship between positive humor and diabetes control will be shown to be bidirectional, with positive humor improving diabetes control, and improved control improving positive humor.
I hypothesize this will also bring psychological and physiological benefits. After all, humor has already been associated with reduced blood glucose levels, reduced microvascular complications, improved heart health, reduced blood pressure, decreased levels of depression and anxiety.
Humor also helps us deal with stress and trauma, so a cause-and-effect relationship makes sense.
Q: Can a positive sense of humor be taught?
A: Absolutely. There is evidence that humor can be developed and strengthened. Paul McGhee, PhD, developed a seven-step humor training program that has been effective in elevating measures of humor across a number of studies.
Others have successfully developed their own protocols, and of course my third study demonstrated a significant increase in both affiliative and self-enhancing humor with training.
Q: Do you think humor training could be incorporated into diabetes care?
A: Humor training programs are easily accessible, incur low to no cost, and are easy to implement. Furthermore, once a person is trained, access to ongoing humor is free, readily available, and fun.
Several diabetes educators have also reported that humor can promote connections, encourage and support diabetes management, galvanize effectiveness, and increase an audience’s attention during education programs.
A version of this article appeared on Medscape.com.
David S. Greene, PhD, associate professor in the department of rehabilitation and human services at the University of Northern Colorado, Greeley, has pioneered research into the field, one previously overlooked when it comes to diabetes management.
This news organization caught up with Dr. Greene to ask about his research along with the implications for diabetes care and for patient well-being.
Question: What prompted you to research the link between humor and diabetes control?
Answer: I was diagnosed with type 1 diabetes in 1966 and consequently have lived with, and studied, various aspects of diabetes for the past 57 years.
For a time, I maintained a small private practice counseling people with diabetes. There I noticed, anecdotally, that my clients’ ability to laugh at, and see the humor in, their diabetes correlated with their emotional adjustment to living with their condition.
While I could find research confirming the physical and psychological benefits of humor in general, I was unable to find any research specifically relating to humor and diabetes.
My new research agenda was born.
Q: What did your research reveal?
A: My first study, published in 2020, found that people living with diabetes displayed the same level of both types of positive, or affiliative and self-enhancing, humor as the norm group used in developing the Humor Styles Questionnaire.
This was a surprising finding given that individuals with diabetes are dealing with a life-altering, chronic illness, with higher rates of depression and anxiety. Moreover, positive humor scores are known to be negatively correlated with depression and anxiety.
While levels of aggressive humor were not altered in my study, people with diabetes did have higher levels of self-defeating humor in my study, which is correlated with psychiatric and somatic concerns, and symptomatology, and so is to be expected.
My second study, published in 2021, examined whether there was a difference between people with diabetes who had an hemoglobin A1c level of 6.99% or less versus those with levels of at least 7% on four disparate types of humor.
The A1c of 6.99% or less group scored significantly higher for both affiliative humor and self-enhancing humor. This implies that better diabetes control is associated with positive humor. This was expected, as was the finding that negative humor was not associated with better control.
On the other hand, there was no significant difference between participants on either type of negative humor, whether aggressive or self-defeating.
Finally, my third study, published in 2023 [with coauthor Nancy D. King, PhD], found that offering humor training to people with type 1 diabetes can strengthen both their affiliative and self-enhancing sense of humor, while leaving their aggressive or self-defeating humor unaffected.
Q: What is ‘positive humor,’ and why do you think it is associated with diabetes control?
A: Both affiliative and self-enhancing humor enhance a person’s sense of self and their relationships with others.
Affiliative humor has been shown to be positively correlated with self-esteem, psychological well-being, social intimacy, and emotional stability. It is also negatively correlated with depression and anxiety.
Self-enhancing humor involves the ability to maintain a humorous outlook on life and to use humor to regulate emotions and as a coping strategy. Like affiliative humor, it is correlated with cheerfulness, self-esteem, optimism, psychological well-being, and life satisfaction. It is negatively related to depression and anxiety.
The preponderance of literature suggests positive humor specifically is associated with buffering many of the risk factors and complications associated with diabetes.
Q: What could underlie the associations between humor and diabetes control?
A: Unfortunately, none of my studies have been able to determine cause and effect, although the most recent one came the closest.
While not reaching statistical significance, the mean reduction in A1c levels from 7.12% at baseline to 6.75% at the post–humor training assessment may very well imply a practical and psychological significance to patients.
I believe, with a larger sample size, significance will be achieved, and that the relationship between positive humor and diabetes control will be shown to be bidirectional, with positive humor improving diabetes control, and improved control improving positive humor.
I hypothesize this will also bring psychological and physiological benefits. After all, humor has already been associated with reduced blood glucose levels, reduced microvascular complications, improved heart health, reduced blood pressure, decreased levels of depression and anxiety.
Humor also helps us deal with stress and trauma, so a cause-and-effect relationship makes sense.
Q: Can a positive sense of humor be taught?
A: Absolutely. There is evidence that humor can be developed and strengthened. Paul McGhee, PhD, developed a seven-step humor training program that has been effective in elevating measures of humor across a number of studies.
Others have successfully developed their own protocols, and of course my third study demonstrated a significant increase in both affiliative and self-enhancing humor with training.
Q: Do you think humor training could be incorporated into diabetes care?
A: Humor training programs are easily accessible, incur low to no cost, and are easy to implement. Furthermore, once a person is trained, access to ongoing humor is free, readily available, and fun.
Several diabetes educators have also reported that humor can promote connections, encourage and support diabetes management, galvanize effectiveness, and increase an audience’s attention during education programs.
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>People with diabetes who have a positive sense of humor appear to have better diabetes control, according to a series of studies that also show patients can be </metaDescription> <articlePDF/> <teaserImage/> <teaser>Several diabetes educators have reported that humor can encourage and support diabetes management, said Dr. David Greene.</teaser> <title>Does laughter offer better blood glucose control?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>15</term> <term>21</term> </publications> <sections> <term canonical="true">39313</term> </sections> <topics> <term canonical="true">205</term> <term>206</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Does laughter offer better blood glucose control?</title> <deck/> </itemMeta> <itemContent> <p><span class="tag metaDescription">People with diabetes who have a positive sense of humor appear to have better diabetes control, according to a series of studies that also show patients can be successfully taught to have a more positive and light-hearted approach.</span> </p> <p>David S. Greene, PhD, associate professor in the department of rehabilitation and human services at the University of Northern Colorado, Greeley, has pioneered research into the field, one previously overlooked when it comes to diabetes management.<br/><br/>This news organization caught up with Dr. Greene to ask about his research along with the implications for diabetes care and for patient well-being.<br/><br/></p> <h2> <strong>Question: What prompted you to research the link between humor and diabetes control?</strong> </h2> <p><strong>Answer:</strong> I was diagnosed with <span class="Hyperlink">type 1 diabetes</span> in 1966 and consequently have lived with, and studied, various aspects of diabetes for the past 57 years.</p> <p>For a time, I maintained a small private practice counseling people with diabetes. There I noticed, anecdotally, that my clients’ ability to laugh at, and see the humor in, their diabetes correlated with their emotional adjustment to living with their condition.<br/><br/>While I could find research confirming the physical and psychological benefits of humor in general, I was unable to find any research specifically relating to humor and diabetes.<br/><br/>My new research agenda was born.<br/><br/></p> <h2> <strong>Q: What did your research reveal?</strong> </h2> <p><strong>A:</strong> My <span class="Hyperlink"><a href="https://diabetesjournals.org/spectrum/article/33/2/175/32927/Diabetes-and-Humor-A-Preliminary-Investigation">first study,</a></span> published in 2020, found that people living with diabetes displayed the same level of both types of positive, or affiliative and self-enhancing, humor as the norm group used in developing the <span class="Hyperlink"><a href="https://humorstyles.com/">Humor Styles Questionnaire.</a></span></p> <p>This was a surprising finding given that individuals with diabetes are dealing with a life-altering, chronic illness, with <a href="https://www.cdc.gov/diabetes/managing/mental-health.html">higher rates of depression and anxiety</a>. Moreover, positive humor scores are known to be negatively correlated with depression and anxiety.<br/><br/>While levels of aggressive humor were not altered in my study, people with diabetes did have higher levels of self-defeating humor in my study, which is correlated with psychiatric and somatic concerns, and symptomatology, and so is to be expected.<br/><br/>My <span class="Hyperlink"><a href="https://diabetesjournals.org/diabetes/article/70/Supplement_1/46-LB/139475/46-LB-Humor-and-A1C-The-Interaction-between-Humor">second study</a></span>, published in 2021, examined whether there was a difference between people with diabetes who had an hemoglobin <span class="Hyperlink">A1c</span> level of 6.99% or less versus those with levels of at least 7% on four disparate types of humor. <br/><br/>The A1c of 6.99% or less group scored significantly higher for both affiliative humor and self-enhancing humor. This implies that better diabetes control is associated with positive humor. This was expected, as was the finding that negative humor was not associated with better control.<br/><br/>On the other hand, there was no significant difference between participants on either type of negative humor, whether aggressive or self-defeating.<br/><br/>Finally, my <span class="Hyperlink"><a href="https://journals.sagepub.com/doi/abs/10.1177/15598276231173912">third study</a></span>, published in 2023 [with coauthor Nancy D. King, PhD], found that offering humor training to people with type 1 diabetes can strengthen both their affiliative and self-enhancing sense of humor, while leaving their aggressive or self-defeating humor unaffected.<br/><br/></p> <h2> <strong>Q: What is ‘positive humor,’ and why do you think it is associated with diabetes control?</strong> </h2> <p><strong>A:</strong> Both affiliative and self-enhancing humor enhance a person’s sense of self and their relationships with others.</p> <p>Affiliative humor has been shown to be positively correlated with self-esteem, psychological well-being, social intimacy, and emotional stability. It is also negatively correlated with depression and anxiety.<br/><br/>Self-enhancing humor involves the ability to maintain a humorous outlook on life and to use humor to regulate emotions and as a coping strategy. Like affiliative humor, it is correlated with cheerfulness, self-esteem, optimism, psychological well-being, and life satisfaction. It is negatively related to depression and anxiety.<br/><br/>The preponderance of literature suggests positive humor specifically is associated with buffering many of the risk factors and complications associated with diabetes.<br/><br/></p> <h2> <strong>Q: What could underlie the associations between humor and diabetes control?</strong> </h2> <p><strong>A:</strong> Unfortunately, none of my studies have been able to determine cause and effect, although the most recent one came the closest.</p> <p>While not reaching statistical significance, the mean reduction in A1c levels from 7.12% at baseline to 6.75% at the post–humor training assessment may very well imply a practical and psychological significance to patients.<br/><br/>I believe, with a larger sample size, significance will be achieved, and that the relationship between positive humor and diabetes control will be shown to be bidirectional, with positive humor improving diabetes control, and improved control improving positive humor.<br/><br/>I hypothesize this will also bring psychological and physiological benefits. After all, humor has already been associated with reduced blood glucose levels, reduced microvascular complications, improved heart health, reduced blood pressure, decreased levels of depression and anxiety.<br/><br/>Humor also helps us deal with stress and trauma, so a cause-and-effect relationship makes sense.<br/><br/></p> <h2> <strong>Q: Can a positive sense of humor be taught?</strong> </h2> <p><strong>A:</strong> Absolutely. There is evidence that humor can be developed and strengthened. <span class="Hyperlink"><a href="https://www.laughterremedy.com/about.dir/about_main.html">Paul McGhee, PhD</a></span>, developed a <span class="Hyperlink">seven-step humor training program</span> that has been effective in elevating measures of humor across a number of studies.</p> <p>Others have successfully developed their own protocols, and of course my third study demonstrated a significant increase in both affiliative and self-enhancing humor with training.<br/><br/></p> <h2> <strong>Q: Do you think humor training could be incorporated into diabetes care?</strong> </h2> <p><strong>A:</strong> Humor training programs are easily accessible, incur low to no cost, and are easy to implement. Furthermore, once a person is trained, access to ongoing humor is free, readily available, and fun.</p> <p>Several diabetes educators have also reported that humor can promote connections, encourage and support diabetes management, galvanize effectiveness, and increase an audience’s attention during education programs.</p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/998462">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Neoadjuvant, adjuvant, or both? The debate in NSCLC rages on
MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.
said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.
Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.
Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.
One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.
Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.
In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).
In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).
Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.
Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.
The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.
Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.
The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.
Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?
The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.
With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.
Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.
The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.
But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?
Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.
For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.
“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.
Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.
A version of this article first appeared on Medscape.com.
MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.
said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.
Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.
Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.
One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.
Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.
In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).
In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).
Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.
Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.
The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.
Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.
The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.
Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?
The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.
With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.
Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.
The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.
But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?
Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.
For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.
“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.
Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.
A version of this article first appeared on Medscape.com.
MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.
said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.
Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.
Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.
One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.
Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.
In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).
In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).
Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.
Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.
The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.
Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.
The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.
Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?
The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.
With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.
Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.
The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.
But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?
Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.
For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.
“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.
Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.
A version of this article first appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant </metaDescription> <articlePDF/> <teaserImage/> <teaser>The question of whether to give upfront immunochemotherapy in resectable non–small cell lung cancer, wait until after surgery, or give both remains a hot topic of debate.</teaser> <title>Neoadjuvant, adjuvant, or both? The debate in NSCLC rages on</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">240</term> <term>270</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Neoadjuvant, adjuvant, or both? The debate in NSCLC rages on</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">MADRID</span> – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.</p> <p><span class="tag metaDescription">Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,”</span> said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.<br/><br/>Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.<br/><br/>Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.<br/><br/>One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.<br/><br/>Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.<br/><br/>In the <a href="https://www.medscape.com/viewarticle/951448">IMpower010 trial</a>, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).<br/><br/>In the <a href="https://www.clinicaltrials.gov/study/NCT02504372">KEYNOTE-091</a> trial, adjuvant pembrolizumab <a href="https://www.medscape.com/viewarticle/971764">significantly improved disease-free survival</a> in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).<br/><br/>Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.<br/><br/>Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.<br/><br/>The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.<br/><br/>Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by <a href="https://www.medscape.com/viewarticle/971977">nearly 14-fold</a> in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.<br/><br/>The <a href="https://www.medscape.com/viewarticle/979006">NADIM II trial</a>, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.<br/><br/>Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?<br/><br/>The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.<br/><br/>With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.<br/><br/>Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.<br/><br/>The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.<br/><br/>But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?<br/><br/>Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.<br/><br/>For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.<br/><br/>“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.<br/><br/>Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.<span class="end"/></p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997790">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
AT ESMO 2023
‘We finally made it’: Amivantamab comes of age in NSCLC
MADRID – , experts said at the annual meeting of the European Society for Medical Oncology (ESMO).
The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.
Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.
Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.
The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.
In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.
The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.
Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).
A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.
The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).
The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.
Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.
Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”
The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
The MARIPOSA trials
The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.
Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.
Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.
Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.
For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).
After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.
The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).
The risk for a second progression was also lower with the combination (HR, 0.75).
Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).
Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.
As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.
Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”
Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.
In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).
Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.
The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.
After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.
This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).
The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.
The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.
Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.
Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.
Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.
Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.
The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.
However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”
“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.
PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.
A version of this article first appeared on Medscape.com.
MADRID – , experts said at the annual meeting of the European Society for Medical Oncology (ESMO).
The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.
Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.
Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.
The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.
In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.
The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.
Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).
A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.
The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).
The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.
Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.
Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”
The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
The MARIPOSA trials
The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.
Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.
Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.
Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.
For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).
After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.
The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).
The risk for a second progression was also lower with the combination (HR, 0.75).
Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).
Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.
As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.
Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”
Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.
In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).
Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.
The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.
After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.
This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).
The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.
The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.
Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.
Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.
Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.
Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.
The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.
However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”
“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.
PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.
A version of this article first appeared on Medscape.com.
MADRID – , experts said at the annual meeting of the European Society for Medical Oncology (ESMO).
The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.
Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.
Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.
The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.
In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.
The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.
Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).
A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.
The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).
The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.
Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.
Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”
The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
The MARIPOSA trials
The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.
Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.
Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.
Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.
For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).
After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.
The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).
The risk for a second progression was also lower with the combination (HR, 0.75).
Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).
Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.
As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.
Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”
Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.
In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).
Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.
The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.
After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.
This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).
The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.
The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.
Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.
Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.
Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.
Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.
The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.
However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”
“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.
PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.
A version of this article first appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>165683</fileName> <TBEID>0C04CEC7.SIG</TBEID> <TBUniqueIdentifier>MD_0C04CEC7</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20231026T153121</QCDate> <firstPublished>20231026T153615</firstPublished> <LastPublished>20231026T153615</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20231026T153615</CMSDate> <articleSource>AT ESMO 2023</articleSource> <facebookInfo/> <meetingNumber>4748-23</meetingNumber> <byline>Liam Davenport</byline> <bylineText>LIAM DAVENPORT</bylineText> <bylineFull>LIAM DAVENPORT</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>New data from three trials evaluating the bispecific antibody amivantamab (Rybrevant) in EGFR-mutated advanced non–small cell lung cancer (NSCLC) have revealed </metaDescription> <articlePDF/> <teaserImage/> <teaser>Data from three trials with amivantamab in advanced EGFR-mutant NSCLC have yielded “exciting” results with experts hailing the drug as standard of care in various settings.</teaser> <title>‘We finally made it’: Amivantamab comes of age in NSCLC</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>chph</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> <term>6</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">240</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>‘We finally made it’: Amivantamab comes of age in NSCLC</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">MADRID</span> – <span class="tag metaDescription">New data from three trials evaluating the bispecific antibody amivantamab (Rybrevant) in EGFR-mutated advanced non–small cell lung cancer (NSCLC) have revealed a clear benefit</span>, experts said at the annual meeting of the European Society for Medical Oncology (ESMO).</p> <p>The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.<br/><br/>Presenting findings from <a href="https://www.clinicaltrials.gov/study/NCT04538664">PAPILLON</a>, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.<br/><br/>Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.<br/><br/>The FDA <a href="https://www.medscape.com/viewarticle/951644">approved amivantamab</a> in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.<br/><br/>In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.<br/><br/>The results, <a href="https://www.nejm.org/doi/10.1056/NEJMoa2306441">simultaneously published</a> in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; <em>P</em> < .0001). This benefit consistently occurred across predefined subgroups.<br/><br/>Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; <em>P</em> = .001).<br/><br/>A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.<br/><br/>The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; <em>P</em> = .106).<br/><br/>The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.<br/><br/>Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.<br/><br/>Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”<br/><br/>The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”<br/><br/></p> <h2>The MARIPOSA trials</h2> <p>The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.</p> <p>Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from <a href="https://www.clinicaltrials.gov/study/NCT04487080">MARIPOSA</a>, which focused on patients with any kind of EGFR mutation.<br/><br/>Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.<br/><br/>Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.<br/><br/>For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).<br/><br/>After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; <em>P</em> < .001) and 18.5 months for those on lazertinib alone.<br/><br/>The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; <em>P</em> < .001).<br/><br/>The risk for a second progression was also lower with the combination (HR, 0.75).<br/><br/>Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; <em>P</em> = .11).<br/><br/>Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.<br/><br/>As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.<br/><br/>Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”<br/><br/>Next up is <a href="https://clinicaltrials.gov/study/NCT04988295">MARIPOSA-2</a>, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.<br/><br/>In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).<br/><br/>Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.<br/><br/>The findings, presented by study investigator Antonio Passaro, MD, PhD, were <a href="https://www.annalsofoncology.org/article/S0923-7534(23)04281-3/fulltext">simultaneously published</a> in Annals of Oncology.<br/><br/>After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.<br/><br/>This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).<br/><br/>The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.<br/><br/>The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.<br/><br/>Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.<br/><br/>Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.<br/><br/>Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.<br/><br/>Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.<br/><br/>The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.<br/><br/>However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”<br/><br/>“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.<br/><br/>PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.</p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997733">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
AT ESMO 2023
Subcutaneous ocrelizumab, ofatumumab ‘reassuring’ in MS
MILAN – , suggest results from two clinical trials.
For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).
After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.
The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.
The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).
Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Anti-CD20–naive
OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.
They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.
In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.
The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.
By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.
The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.
However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.
Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”
He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
Efficacy maintained
The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.
After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.
Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.
The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.
At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.
The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.
They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
Reassuring results
“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.
“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.
“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.
“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.
In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”
OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.
A version of this article first appeared on Medscape.com.
MILAN – , suggest results from two clinical trials.
For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).
After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.
The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.
The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).
Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Anti-CD20–naive
OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.
They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.
In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.
The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.
By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.
The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.
However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.
Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”
He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
Efficacy maintained
The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.
After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.
Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.
The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.
At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.
The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.
They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
Reassuring results
“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.
“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.
“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.
“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.
In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”
OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.
A version of this article first appeared on Medscape.com.
MILAN – , suggest results from two clinical trials.
For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).
After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.
The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.
The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).
Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Anti-CD20–naive
OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.
They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.
In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.
The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.
By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.
The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.
However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.
Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”
He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
Efficacy maintained
The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.
After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.
Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.
The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.
At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.
The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.
They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
Reassuring results
“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.
“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.
“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.
“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.
In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”
OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.
A version of this article first appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Subcutaneous administration of anti-CD20 monoclonal antibody therapy offers ongoing clinical efficacy in the management of patients with relapsing and primary p</metaDescription> <articlePDF/> <teaserImage/> <teaser>The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do.” </teaser> <title>Subcutaneous ocrelizumab, ofatumumab ‘reassuring’ in MS</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>nr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Neurology Reviews</journalTitle> <journalFullTitle>Neurology Reviews</journalFullTitle> <copyrightStatement>2018 Frontline Medical Communications Inc.,</copyrightStatement> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>msrc</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> </publications_g> <publications> <term canonical="true">22</term> <term>21</term> <term>59347</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">251</term> <term>258</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Subcutaneous ocrelizumab, ofatumumab ‘reassuring’ in MS</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">MILAN – </span><span class="tag metaDescription">Subcutaneous administration of anti-CD20 monoclonal antibody therapy offers ongoing clinical efficacy in the management of patients with relapsing and primary progressive <a href="https://emedicine.medscape.com/article/1146199-overview">multiple sclerosis</a> (MS)</span>, suggest results from two clinical trials.</p> <p>For <a href="https://classic.clinicaltrials.gov/ct2/show/NCT05232825">OCARINA II</a>, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody <a href="https://reference.medscape.com/drug/ocrevus-ocrelizumab-1000112">ocrelizumab</a> (Ocrevus).<br/><br/>After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.<br/><br/>The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.<br/><br/>The second study, <a href="https://classic.clinicaltrials.gov/ct2/show/NCT04486716">OLIKOS</a>, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: <a href="https://reference.medscape.com/drug/arzerra-ofatumumab-999309">ofatumumab</a> (Arzerra).<br/><br/>Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.<br/><br/>The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.<br/><br/></p> <h2>Anti-CD20–naive</h2> <p>OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.</p> <p>They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.<br/><br/>In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.<br/><br/>The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.<br/><br/>By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.<br/><br/>The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.<br/><br/>However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.<br/><br/>Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”<br/><br/>He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”<br/><br/></p> <h2>Efficacy maintained</h2> <p>The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or <a href="https://reference.medscape.com/drug/rituxan-hycela-rituximab-342243">rituximab</a> and who had an EDSS score ≤ 5.5 and were neurologically stable.</p> <p>After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.<br/><br/>Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.<br/><br/>The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.<br/><br/>At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.<br/><br/>The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.<br/><br/>They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.<br/><br/></p> <h2>Reassuring results</h2> <p>“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.</p> <p>“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.<br/><br/>“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.<br/><br/>“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.<br/><br/>In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”<br/><br/>OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.<span class="end"/></p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997741">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
AT ECTRIMS 2023
Lag in antidepressant treatment response explained?
BARCELONA – , new imaging data suggest.
In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.
The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.
First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.
“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.
The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
Marked increase in synaptic density
SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.
For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.
They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.
Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.
When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).
However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.
Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).
In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.
“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
Exciting but not conclusive
Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.
“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.
Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.
Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.
Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”
Dr. Nutt added that the results provide further evidence that “enhancing serotonin function in the brain can have enduring health benefits.”
Funding support was provided by the Danish Council for Independent Research, the Lundbeck Foundation, Rigshospitalet, and the Swedish Research Council. Open access funding provided by Royal Library, Copenhagen University Library.
Dr. Knudsen declares relationships with Sage Biogen, H. Lundbeck, Onsero, Pangea, Gilgamesh, Abbvie, and PureTechHealth. Another author declares relationships with Cambridge Cognition and PopReach via Cambridge Enterprise.
A version of this article first appeared on Medscape.com.
BARCELONA – , new imaging data suggest.
In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.
The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.
First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.
“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.
The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
Marked increase in synaptic density
SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.
For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.
They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.
Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.
When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).
However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.
Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).
In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.
“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
Exciting but not conclusive
Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.
“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.
Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.
Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.
Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”
Dr. Nutt added that the results provide further evidence that “enhancing serotonin function in the brain can have enduring health benefits.”
Funding support was provided by the Danish Council for Independent Research, the Lundbeck Foundation, Rigshospitalet, and the Swedish Research Council. Open access funding provided by Royal Library, Copenhagen University Library.
Dr. Knudsen declares relationships with Sage Biogen, H. Lundbeck, Onsero, Pangea, Gilgamesh, Abbvie, and PureTechHealth. Another author declares relationships with Cambridge Cognition and PopReach via Cambridge Enterprise.
A version of this article first appeared on Medscape.com.
BARCELONA – , new imaging data suggest.
In a double-blind study, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.
The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.
First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.
“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.
The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and simultaneously published online in Molecular Psychiatry.
Marked increase in synaptic density
SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.
For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.
They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.
Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.
When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (P = .41) or in the hippocampus (P = .26).
However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.
Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; P = .003) and the hippocampus (rp value, 0.41; P = .048).
In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; P = .95) or the hippocampus (rp value, –0.06; P = .62) in the hippocampus.
“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.
Exciting but not conclusive
Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.
“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.
Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.
Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.
Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”
Dr. Nutt added that the results provide further evidence that “enhancing serotonin function in the brain can have enduring health benefits.”
Funding support was provided by the Danish Council for Independent Research, the Lundbeck Foundation, Rigshospitalet, and the Swedish Research Council. Open access funding provided by Royal Library, Copenhagen University Library.
Dr. Knudsen declares relationships with Sage Biogen, H. Lundbeck, Onsero, Pangea, Gilgamesh, Abbvie, and PureTechHealth. Another author declares relationships with Cambridge Cognition and PopReach via Cambridge Enterprise.
A version of this article first appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The typical lag between treatment initiation with selective serotonin reuptake inhibitors (SSRIs) for depression and enhanced mood may be because of the time it</metaDescription> <articlePDF/> <teaserImage>244357</teaserImage> <teaser>Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density.</teaser> <title>Lag in antidepressant treatment response explained?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>cpn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">9</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">202</term> <term>258</term> <term>61423</term> <term>248</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400bde9.jpg</altRep> <description role="drol:caption">Dr. Oliver Howes</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400f63c.jpg</altRep> <description role="drol:caption">Dr. David Nutt</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Lag in antidepressant treatment response explained?</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">BARCELONA </span>–<span class="dateline"> </span><span class="tag metaDescription">The typical lag between treatment initiation with selective serotonin reuptake inhibitors (SSRIs) for depression and enhanced mood may be because of the time it takes to increase brain synaptic density</span>, new imaging data suggest.</p> <p><a href="https://classic.clinicaltrials.gov/ct2/show/NCT04239339">In a double-blind study</a>, more than 30 volunteers were randomly assigned to the SSRI escitalopram or placebo for 3-5 weeks. Using PET imaging, the investigators found that over time, synaptic density significantly increased significantly in the neocortex and hippocampus but only in patients taking the active drug.<br/><br/>The results point to two conclusions, said study investigator Gitta Moos Knudsen, MD, PhD, clinical professor and chief physician at the department of clinical medicine, neurology, psychiatry and sensory sciences at Copenhagen (Denmark) University Hospital.<br/><br/>First, they indicate that SSRIs increase synaptic density in brain areas critically involved in depression, a finding that would go some way to indicating that the synaptic density in the brain may be involved in how antidepressants function, “which would give us a target for developing novel drugs against depression,” said Dr. Knudsen.<br/><br/>“Secondly, our data suggest synapses build up over a period of weeks, which would explain why the effects of these drugs take time to kick in,” she added.<br/><br/>The findings were presented at the 36th European College of Neuropsychopharmacology (ECNP) Congress and <a href="https://www.nature.com/articles/s41380-023-02285-8">simultaneously published</a> online in Molecular Psychiatry.<br/><br/></p> <h2>Marked increase in synaptic density</h2> <p>SSRIs are widely used for depression as well as anxiety and obsessive-compulsive disorder. It is thought that they act via neuroplasticity and synaptic remodeling to improve cognition and emotion processing. However, the investigators note clinical evidence is lacking.</p> <p>For the study, the researchers randomly assigned healthy individuals to either 20-mg escitalopram or placebo for 3-5 weeks.<br/><br/>They performed PET with the 11C-UCB-J tracer, which allows imaging of the synaptic vesicle glycoprotein 2A (SV2A) in the brain, synaptic density, as well as changes in density over time, in the hippocampus and neocortex.<br/><br/>Between May 2020 and October 2021, 17 individuals were assigned to escitalopram and 15 to placebo. There were no significant differences between two groups in terms of age, sex, and PET-related variables. Serum escitalopram measurements confirmed that all participants in the active drug group were compliant.<br/><br/>When synaptic density was assessed at a single time point, an average of 29 days after the intervention, there were no significant differences between the escitalopram and placebo groups in either the neocortex (<em>P</em> = .41) or in the hippocampus (<em>P</em> = .26).<br/><br/>However, when they performed a secondary analysis of the time-dependent effect on SV2A levels, they found a marked difference between the two study groups.<br/><br/>Compared with the placebo group, participants taking escitalopram had a marked increase in synaptic density in both the neocortex (rp value, 0.58; <em>P</em> = .003) and the hippocampus (rp value, 0.41; <em>P</em> = .048).<br/><br/>In contrast, there were no significant changes in synaptic density in either the neocortex (rp value, –0.01; <em>P</em> = .95) or the hippocampus (rp value, –0.06; <em>P</em> = .62) in the hippocampus.<br/><br/>“That is consistent with our clinical observation that it takes time to evolve synaptic density, along with clinical improvement. Does that mean that the increase in synaptic density is a precondition for improvement in symptoms? We don’t know,” said Dr. Knudsen.<br/><br/></p> <h2>Exciting but not conclusive</h2> <p>Session co-chair Oliver Howes, MD, PhD, professor of molecular psychiatry, King’s College London, agreed that the results do not prove the gradual increase in synaptic density the treatment response lag with SSRIs.[[{"fid":"244357","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Oliver Howes of Kings College, London","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Oliver Howes"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]</p> <p>“We definitely don’t yet have all the data to know one way or the other,” he said in an interview.<br/><br/>Another potential hypothesis, he said, is that SSRIs are causing shifts in underlying brain circuits that lead to cognitive changes before there is a discernable improvement in mood.<br/><br/>Indeed, Dr. Howes suggested that increases in synaptic density and cognitive changes related to SSRI use are not necessarily dependent on each other and could even be unrelated.<br/><br/>Also commenting on the research, David Nutt, MD, PhD, Edmond J. Safra professor of neuropsychopharmacology at Imperial College London, said that the “delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So, these new data in humans, that use cutting edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts, are very exciting.”[[{"fid":"274181","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. David Nutt","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. David Nutt"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>Dr. Nutt added that the results provide further evidence that “enhancing serotonin function in the brain can have enduring health benefits.”<br/><br/>Funding support was provided by the Danish Council for Independent Research, the Lundbeck Foundation, Rigshospitalet, and the Swedish Research Council. Open access funding provided by Royal Library, Copenhagen University Library.<br/><br/>Dr. Knudsen declares relationships with Sage Biogen, H. Lundbeck, Onsero, Pangea, Gilgamesh, Abbvie, and PureTechHealth. Another author declares relationships with Cambridge Cognition and PopReach via Cambridge Enterprise.<span class="end"/></p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997413">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
AT ECNP 2023
‘Why did I choose this?’ Tackling burnout in oncology
MADRID – “Why did I choose this?”
That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.
“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.
This oncologist is hardly alone.
A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.
This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.
More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.
Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.
The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.
Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.
Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.
Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.
“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.
While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.
In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.
A panel of experts at the meeting touched on some of these solutions.
Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.
Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.
“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”
The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.
However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”
But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”
In other words, oncologists need to be able to set boundaries and say no.
Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.
Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
MADRID – “Why did I choose this?”
That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.
“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.
This oncologist is hardly alone.
A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.
This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.
More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.
Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.
The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.
Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.
Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.
Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.
“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.
While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.
In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.
A panel of experts at the meeting touched on some of these solutions.
Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.
Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.
“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”
The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.
However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”
But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”
In other words, oncologists need to be able to set boundaries and say no.
Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.
Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
MADRID – “Why did I choose this?”
That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.
“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.
This oncologist is hardly alone.
A survey from ESMO conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.
This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.
More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.
Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.
The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.
Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.
Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.
Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.
“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.
While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.
In response to this chronic and growing problem, ESMO launched its Resilience Task Force in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.
A panel of experts at the meeting touched on some of these solutions.
Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.
Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.
“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”
The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.
However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”
But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”
In other words, oncologists need to be able to set boundaries and say no.
Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.
Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.
A version of this article first appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>165657</fileName> <TBEID>0C04CE27.SIG</TBEID> <TBUniqueIdentifier>MD_0C04CE27</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20231025T140120</QCDate> <firstPublished>20231025T140907</firstPublished> <LastPublished>20231025T140907</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20231025T140906</CMSDate> <articleSource>FROM ESMO 2023</articleSource> <facebookInfo/> <meetingNumber>4748-23</meetingNumber> <byline>Liam Davenport</byline> <bylineText>LIAM DAVENPORT</bylineText> <bylineFull>LIAM DAVENPORT</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Rates of burnout among oncologists remain alarmingly high, explained session chair Kok Haw Jonathan Lim, MD, PhD.</metaDescription> <articlePDF/> <teaserImage/> <teaser>Building a sustainable oncology workforce will not be easy, but improving staffing shortages and integrating resilience training can help, experts say.</teaser> <title>‘Why did I choose this?’ Tackling burnout in oncology</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">278</term> <term>27442</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>‘Why did I choose this?’ Tackling burnout in oncology</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">MADRID</span> – “Why did I choose this?”</p> <p>That is the core question a Portuguese oncologist posed from the audience during a session at the annual meeting of the European Society for Medical Oncology (ESMO) that was dedicated to building a sustainable oncology workforce.<br/><br/>“Ten, twenty years ago, being a doctor was a dream,” she said, but right now doctors are underpaid, under strain, and have very few resources.<br/><br/>This oncologist is hardly alone.<br/><br/><span class="tag metaDescription">Rates of burnout among oncologists remain alarmingly high, explained session chair Kok Haw Jonathan Lim, MD, PhD.</span><br/><br/>A <a href="https://www.annalsofoncology.org/article/S0923-7534(19)32281-1/fulltext">survey from ESMO</a> conducted almost a decade ago found that more than 50% of oncologists across Europe, many of whom were early in their careers, reported being burned out.<br/><br/>This, Dr. Lim said, “was the starting point,” well before the COVID pandemic struck.<br/><br/>More recently, the pandemic has taken its own toll on the well-being of oncologists. A survey presented at ESMO 2020 revealed that 38% of participants, spanning 101 countries, reported experiencing burnout, and 66% said they were not able to perform their job.<br/><br/>Medscape’s 2023 Physician Burnout and Depression Report highlighted similar burnout rates, with 53% of U.S. physicians and 52% of oncologists saying they felt burned out, compared with about 42% in 2018, before the pandemic.<br/><br/>The oncology workforce is in crisis in every country, said Dr. Lim, from the Cancer Dynamics Lab, the Francis Crick Institute, London.<br/><br/>Burnout, characterized by emotional exhaustion, depersonalization or feelings of cynicism, and a low sense of personal accomplishment, can result in a poor work-life balance as well as poor mental and physical health. Factors linked to burnout include social isolation, increased workload, reduced quality of work, lack of control over work, and stressful professional experiences.<br/><br/>Together, these factors can affect patient care and further exacerbate staffing issues, Dr. Lim said.<br/><br/>Staffing shortages are common. Oncologists often work long hours or on weekends to cover gaps caused by staffing shortages. Recent data revealed that in high-income countries, there are on average 0.65 medical oncologists and 0.25 radiation oncologists per 100 patients — a situation made worse by professionals taking early retirement or leaving medicine during the pandemic.<br/><br/>“We have seen that the shortage of human resources in many countries as well as the increasing workload related to the increasing number of cancers,” as well as patients surviving longer, have increased pressures on the healthcare system, Andrés Cervantes, MD, PhD, president of ESMO, explained in a press conference.<br/><br/>While tackling these oncology workforce problems requires smaller, local changes to a physician’s daily routine, “the real change,” Dr. Lim said, lies at an infrastructure level.<br/><br/>In response to this chronic and growing problem, ESMO launched its <a href="https://www.esmo.org/career-development/resilience-task-force">Resilience Task Force</a> in 2020 to evaluate burnout and well-being. The task force plans to publish a position paper in which it will propose a set of recommendations regarding the psychosocial risks of burnout as well as flexible work patterns, well-being resources, and targeted support.<br/><br/>A panel of experts at the meeting touched on some of these solutions.<br/><br/>Dealing with staff shortages is a must, said Jean-Yves Blay, MD, PhD, during the session. “It’s a simple mathematical equation,” Dr. Blay said. “We must increase the number of doctors in medical schools and the number of nurses and healthcare professionals in all schools.” Improving staffing would also help reduce chronic workload issues.<br/><br/>Resilience training should also be incorporated into physician training starting in medical school. Teaching oncologists how to deal with bad news and to cope when patients dies is particularly important.<br/><br/>“I was not taught that,” said the oncologist from Portugal. “I had to learn that at my own cost.”<br/><br/>The good news is that it’s possible to develop resiliency skills over time, said Claire Hardy, PhD, from Lancaster University, United Kingdom, who agreed that training programs could be one approach to improve oncologists’ work life.<br/><br/>However, a person’s needs are determined by their institution and personal responsibilities. “No one knows your job better than you,” Dr. Hardy said. “No one knows better than you where the inefficiencies are, where the bureaucracy is that could be taken away, or it could be done by somebody whose role it is to sort all that out.”<br/><br/>But having this understanding is not enough. Physician also need to feel “psychological safety to be able to speak out and say that something isn’t working right now or is too much,” or, “I’m spending too much time doing this.”<br/><br/>In other words, oncologists need to be able to set boundaries and say no.<br/><br/>Dr. Hardy said this concept “has been around a while, but it’s really gaining momentum,” and being able to discuss these issues in a forum such as the ESMO Congress is a promising start.<br/><br/>Dr. Lim has relationships with Janseen and SEOM. No other relevant financial relationships were disclosed.<span class="end"/></p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997683">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM ESMO 2023
‘Frame running’ may help boost physical activity in MS
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>A specially adapted frame to support individuals with walking and balance disabilities could help people with multiple sclerosis engage in moderate to vigorous </metaDescription> <articlePDF/> <teaserImage/> <teaser>‘Frame running’ uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.</teaser> <title>‘Frame running’ may help boost physical activity in MS</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>msrc</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> <publicationData> <publicationCode>nr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Neurology Reviews</journalTitle> <journalFullTitle>Neurology Reviews</journalFullTitle> <copyrightStatement>2018 Frontline Medical Communications Inc.,</copyrightStatement> </publicationData> </publications_g> <publications> <term>59347</term> <term canonical="true">22</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">251</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>‘Frame running’ may help boost physical activity in MS</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">MILAN</span> – <span class="tag metaDescription">A specially adapted frame to support individuals with walking and balance disabilities could help people with multiple sclerosis engage in moderate to vigorous physical activity and improve their physical function</span>, a pilot study suggests.</p> <p>“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.<br/><br/>Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.<br/><br/>“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.<br/><br/>It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”<br/><br/>The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.<br/><br/></p> <h2>Dearth of exercise opportunities</h2> <p>The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.</p> <p>This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”<br/><br/>In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.<br/><br/>The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.<br/><br/>The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.<br/><br/>The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.<br/><br/></p> <h2>The camaraderie of physical activity</h2> <p>With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.</p> <p>The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).<br/><br/>There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.<br/><br/>A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.<br/><br/>The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”<br/><br/></p> <h2>Mix of physical interventions</h2> <p>Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.</p> <p>He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”<br/><br/>However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”<br/><br/>With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”<br/><br/>Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.<br/><br/>Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”<br/><br/>The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.<span class="end"/></p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997650">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM ECTRIMS 2023
Recombinant IL-2 shows potential in atopic dermatitis
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
[embed:render:related:node:264060]
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
[embed:render:related:node:264060]
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.
The research was presented at the annual congress of the European Academy of Dermatology and Venereology.
, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.
“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.
“For me, this is proof of concept for so many things, and it gets me very excited.”
Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”
He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”
Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.
Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”
Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”
He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”
At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.
Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.
Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”
To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.
Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.
[embed:render:related:node:264060]
The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.
Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.
Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.
The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.
By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).
Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.
There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.
The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).
Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.
A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.
Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.
Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.
The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.
The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.
Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.
A version of this article appeared on Medscape.com.
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This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>More than 40 patients were randomly assigned to receive one of two dosages of a highly selective recombinant interleukin (IL)-2 conjugate, rezpegaldesleukin, or</metaDescription> <articlePDF/> <teaserImage/> <title>Recombinant IL-2 shows potential in atopic dermatitis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>skin</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">13</term> <term>21</term> <term>15</term> </publications> <sections> <term canonical="true">39313</term> <term>53</term> </sections> <topics> <term canonical="true">189</term> <term>203</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Recombinant IL-2 shows potential in atopic dermatitis</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">BERLIN</span> – A novel regulatory T cell–stimulating therapy appears to significantly improve <span class="Hyperlink">atopic dermatitis</span> in patients with moderate to severe disease and may even benefit quality of life, suggest results from a <span class="Hyperlink"><a href="https://clinicaltrials.gov/study/NCT04081350">phase 1b trial</a></span>.</p> <p>The research was presented at the annual congress of the European Academy of Dermatology and Venereology.<br/><br/><span class="tag metaDescription">More than 40 patients were randomly assigned to receive one of two dosages of a highly selective recombinant interleukin (IL)-2 conjugate, rezpegaldesleukin, or placebo for 12 weeks</span>, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.<br/><br/>“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.<br/><br/>“For me, this is proof of concept for so many things, and it gets me very excited.”<br/><br/>Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”<br/><br/>He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”<br/><br/>Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.<br/><br/><span class="Hyperlink">Tiago dos Reis Matos, MD, PhD, MSc</span>, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”<br/><br/>Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”<br/><br/>He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.” <br/><br/>At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.<br/><br/>Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with <span class="Hyperlink">conjunctivitis</span>, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.<br/><br/>Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”<br/><br/>To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.<br/><br/>Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.<br/><br/>The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.<br/><br/>Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.<br/><br/>Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.<br/><br/>The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.<br/><br/>By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (<em>P</em> = .002 for the higher dose vs. placebo).<br/><br/>Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.<br/><br/>There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.<br/><br/>The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (<em>P</em> = .0158 for the higher dose vs. placebo).<br/><br/>Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.<br/><br/>A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.<br/><br/>Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.<br/><br/>Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.<br/><br/>The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.<br/><br/>The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.<br/><br/>Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.<span class="end"><br/><br/></span></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997475">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p>Rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development</p> </itemContent> </newsItem> </itemSet></root>
AT THE EADV CONGRESS
Chemo-immunotherapy good, adding a PARP inhibitor better in endometrial cancer?
MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.
In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.
– 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.
In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.
The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.
Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.
However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
Inside AtTEnd
A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.
David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”
The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.
This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.
To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.
Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.
The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.
The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.
Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.
In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).
A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.
Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).
Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”
Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.
But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
Inside DUO-E
The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.
The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.
Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.
Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.
About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.
Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).
This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).
In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).
Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).
However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.
Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.
But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”
So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.
AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.
DUO-E was funded by AstraZeneca.
Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.
Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.
Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.
Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.
A version of this article first appeared on Medscape.com.
MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.
In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.
– 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.
In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.
The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.
Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.
However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
Inside AtTEnd
A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.
David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”
The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.
This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.
To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.
Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.
The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.
The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.
Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.
In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).
A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.
Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).
Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”
Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.
But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
Inside DUO-E
The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.
The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.
Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.
Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.
About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.
Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).
This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).
In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).
Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).
However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.
Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.
But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”
So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.
AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.
DUO-E was funded by AstraZeneca.
Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.
Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.
Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.
Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.
A version of this article first appeared on Medscape.com.
MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.
In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.
– 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.
In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.
The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.
Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.
However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
Inside AtTEnd
A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.
David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”
The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.
This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.
To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.
Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.
The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.
The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.
Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.
In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).
A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.
Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).
Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”
Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.
But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
Inside DUO-E
The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.
The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.
Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.
Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.
About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.
Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).
This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).
In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).
Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).
However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.
Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.
But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”
So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.
AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.
DUO-E was funded by AstraZeneca.
Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.
Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.
Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.
Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.
A version of this article first appeared on Medscape.com.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>165614</fileName> <TBEID>0C04CD39.SIG</TBEID> <TBUniqueIdentifier>MD_0C04CD39</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20231023T141551</QCDate> <firstPublished>20231023T155259</firstPublished> <LastPublished>20231023T155259</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20231023T155259</CMSDate> <articleSource>FROM ESMO 2023</articleSource> <facebookInfo/> <meetingNumber>4748-23</meetingNumber> <byline>Liam Davenport</byline> <bylineText>LIAM DAVENPORT</bylineText> <bylineFull>LIAM DAVENPORT</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Adding immunotherapy to chemotherapy improved progression-free survival (PFS) among all-comers</metaDescription> <articlePDF/> <teaserImage/> <title>Chemo-immunotherapy good, adding a PARP inhibitor better in endometrial cancer?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">217</term> <term>270</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Chemo-immunotherapy good, adding a PARP inhibitor better in endometrial cancer?</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">MADRID – </span>Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.</p> <p>In the <a href="https://clinicaltrials.gov/study/NCT03603184">AtTEnd</a> trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.<br/><br/><span class="tag metaDescription">Adding immunotherapy to chemotherapy improved progression-free survival (PFS) among all-comers</span> – 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.<br/><br/>In the <a href="https://clinicaltrials.gov/study/NCT04269200">DUO-E</a> trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.<br/><br/>The results, <a href="https://ascopubs.org/doi/10.1200/JCO.23.02132">published simultaneously</a> in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.<br/><br/>Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.<br/><br/>However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor. <br/><br/></p> <h2>Inside AtTEnd</h2> <p>A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.</p> <p>David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”<br/><br/>The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.<br/><br/>This approach was borne out by recent <a href="https://www.nejm.org/doi/10.1056/NEJMoa2302312">positive PFS results</a> from the <a href="https://clinicaltrials.gov/study/NCT03914612">NRG-GY018</a> trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the <a href="https://clinicaltrials.gov/study/NCT03981796">RUBY</a> trial of dostarlimab in <a href="https://www.nejm.org/doi/10.1056/NEJMoa2216334">primary advanced or recurrent disease.</a><br/><br/>To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.<br/><br/>Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.<br/><br/>The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.<br/><br/>The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.<br/><br/>Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; <em>P</em> = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.<br/><br/>In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; <em>P</em> = .0219).<br/><br/>A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; <em>P</em> = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.<br/><br/>Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).<br/><br/>Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”<br/><br/>Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.<br/><br/>But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”<br/><br/></p> <h2>Inside DUO-E</h2> <p>The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.</p> <p>The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.<br/><br/>Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.<br/><br/>Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.<br/><br/>About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.<br/><br/>Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; <em>P</em> = .003; and HR, 0.55; <em>P</em> < .0001, respectively).<br/><br/>This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).<br/><br/>In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).<br/><br/>Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).<br/><br/>However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.<br/><br/>Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.<br/><br/>But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.<br/><br/>“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”<br/><br/>So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.<br/><br/>AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.<br/><br/>DUO-E was funded by AstraZeneca.<br/><br/>Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.<br/><br/>Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.<br/><br/>Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.<br/><br/>Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.<span class="end"/></p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997607">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p>Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients.”</p> </itemContent> </newsItem> </itemSet></root>
FROM ESMO 2023