Nick Mulcahy

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

A version of this article originally appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Among adults who drink alcohol at relatively high amounts, regular weekly physical activity may reduce the mortality risk posed by alcohol-related cancers, concludes a new observational study involving 50,000-plus British adults.

Being physically active – for example, by walking, house cleaning, or playing a sport – could be promoted as a risk-minimization measure for alcohol-related cancers, say the authors, led by Emmanuel Stamatakis, PhD, professor of Physical Activity, Lifestyle, and Population Health, University of Sydney, Australia.

The researchers found a “strong direct association between alcohol consumption and mortality risk of [10] alcohol-related cancers.”

Specifically, when compared with never drinkers, there was a significantly higher risk of dying from such cancers among drinkers who consumed “hazardous” and “harmful” amounts of alcohol, and also for ex-drinkers.

Notably, occasional drinkers and drinkers within guidelines did not have statistically significantly higher risks for alcohol-related cancer mortality.

But the analysis also found that among the bigger drinkers, the risks were “substantially attenuated” in physically active participants who met at least the lower recommended limit of activity (>7.5 metabolic equivalent task [MET]–hours/week).

That’s not a taxing amount of activity because, for example, general household cleaning results in 3 METs/hour and walking slowly translates into 2 METs/hour. However, nearly a quarter of survey participants reported no physical activity.

The study was published online May 14 in the International Journal of Cancer.

The new results require confirmation because the findings “are limited in their statistical power,” with small numbers of cases in several categories, said Alpa Patel, PhD, an epidemiologist at the American Cancer Society, who was not involved in the study. For example, there were only 55 alcohol-related cancer deaths among the 1540 harmful drinkers.

Patel stressed that, “based on the collective evidence to date, it is best to both avoid alcohol consumption and engage in sufficient amounts of physical activity.” That amount is 150-300 minutes of moderate or 75-150 minutes of vigorous activity per week for cancer prevention.

Her message about abstinence is in-line with new ACS guidelines issued last month, as reported by Medscape Medical News. The ACS’s guidance was criticized by many readers in the comments section, who repeatedly encouraged “moderation.”

However, the ACS also recommended moderation, saying, for those adults who do drink, intake should be no more than 1 drink/day for women or 2 drinks/day for men. 

Study author Dr. Stamatakis commented on the alcohol debate.

“Any advice for complete abstinence is bound to alienate many people,” he told Medscape Medical News in an email. “Alcohol drinking has been an integral part of many societies for thousands of years.”

Dr. Stamatakis, who is an occasional beer drinker, also said, “there is no healthy level of alcohol drinking.”

This was also the conclusion of a 2018 study published in the Lancet, which stated that there is “no safe limit,” as even one drink a day increases the risk of cancer. A few years earlier, the 2014 World Cancer Report found a dose-response relationship between alcohol consumption and certain cancers.

However, epidemiological findings are not necessarily “clinically relevant,” commented Jennifer Ligibel, MD, a medical oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, in a 2018 interview with Medscape Medical News.

Dr. Ligibel explained that there are 50 years of studies linking alcohol and cancers. “With the huge amount of data we have, even small differences [in consumption] are statistically significant.”

Dr. Ligibel cited an often-repeated statistic: for the average woman, there is a 12% lifetime risk of breast cancer. “If a woman consumes a drink a day, which is considered a low-level intake, that risk may become about 13% – which is statistically significant,” Dr. Ligibel explained.

But that risk increase is not clinically relevant, she added.

Mean 10 years of follow-up

The new study is the first to examine physical activity, drinking, and the 10 cancers that have been linked to alcohol consumption (oral cavity, throat, larynx, esophagus, liver, colorectal, stomach, breast, pancreas, and lung).

The authors used data from 10 British population-based health surveys from 1994-2008 and looked at adults aged 30 years and older. The mean follow-up period was 9.9 years.

Among 54,686 participants, there were 2039 alcohol-related site-specific cancer deaths.

Alcohol consumption categories were based on U.K. guidelines, with 1 unit equal to 8 grams (about 2 ounces) of pure alcohol. The categories were as follows: drinking within guidelines (<14 units/week for women, <21 units/week for men), hazardous level (14-35 units/week for women, 21-49 units/week for men), and harmful level (> 35 units/week for women, >49 units/week for men). The survey also queried participants about being ex-drinkers, occasional drinkers, and never drinkers.

Physical activity was assessed using self-reported accounts of the 4 weeks preceding the health survey and intensity of activity (light, moderate, or vigorous) was queried. Physical activity was categorized using the upper (15 MET-hours/week) and lower (the aforementioned <7 MET-hours/week) recommended limits.

The median age of participants was 51 years; 7.9% were never drinkers and 14.7% exceeded guideline amounts. For physical activity, 23% reported none. The median level of activity was 9 MET-hours/week.

The authors say that the “increased risks [among the harmful, hazardous, and ex-drinker categories] were eliminated” among the individuals who reported physical activity >7.5 MET-hours/week. That meant the hazard ratios for cancer mortality for each category were reduced to the point that they were no longer statistically significant.

For example, for all drinkers in the “hazardous” category, the risk of cancer-related mortality was significantly higher than for nondrinkers (with a hazard ratio of 1.39), but in the subgroup of these participants who were physically active at the lower recommended limit, the hazard ratio dropped to 1.21.

These “broad patterns of effect modification by physical activity persisted when the upper physical activity limit [15 MET-hours/week] was used,” write the authors.

The new study adds to the literature on cancer mortality and alcohol consumption. In another recent study, researchers looked at eight British cohorts and reported overall cancer mortality associated with alcohol consumption was eliminated among those meeting physical activity recommendations (Br J Sports Med. 2017;51:651-7). The new study added two more cohorts to this base of eight and only focused on cancers that have been linked to alcohol consumption. The earlier study included deaths from all types of cancer.

The refinement of focus in the current study is important, say Dr. Stamatakis and colleagues.

“This specificity adds biological plausibility and permits a more immediate translation of our findings into policy and practice,” they write. 

Dr. Stamatakis practices what he advocates, but is not a teetotaler.

“I exercise (e.g., dynamic yoga, HIIT cardio workouts, run, cycle, lift weights) for 45-60 minutes a day and I walk 8,000-14,000 steps daily. That would categorize me perhaps in the top 3%-5% for my age/sex group. And I enjoy 1-2 cans of craft beer a couple of times a week,” he said in an email.

Dr. Stamatakis and Dr. Patel have reported no relevant financial relationships.

This article first appeared on Medscape.com.

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.

The Food and Drug Administration approved a combination of pertuzumab (Perjeta, Genentech/Roche), trastuzumab (Herceptin, Genentech/Roche) and hyaluronidase (Phesgo, Genentech/Roche) that is administered subcutaneously – rather than intravenously – for the treatment of early and metastatic HER2-positive breast cancers.

Phesgo is initially used in combination with chemotherapy at an infusion center but could continue to be administered in a patient’s home by a qualified health care professional once chemotherapy is complete, according to the FDA.

Administration takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for maintenance doses, according to a Genentech press statement. This compares favorably with the 150 minutes needed for the combined loading dose of intravenous pertuzumab and trastuzumab, and the 60-150 minutes for intravenous maintenance infusions, the company said.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in an agency press release.

“The fixed-dose combination of trastuzumab and pertuzumab offers a simpler, faster, and easier treatment experience for patients with HER2-positive breast cancer,” said Antoinette Tan, MD, MHSc, chief of breast medical oncology at Levine Cancer Institute, Charlotte, N.C., in the company statement.

Dr. Tan also said that home administration “can be advantageous for patients and infusion centers.”

However, in April, the Community Oncology Alliance strenuously objected to this type of treatment in a patient’s home, as reported by Medscape Medical News.

The group, which represents U.S. community-based practices, said it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The FDA’s approval was based on the results of the pivotal phase 3 FeDeriCa trial, a noninferiority study in patients with HER2-positive early breast cancer, which demonstrated that the new product had comparable efficacy and safety as intravenous pertuzumab and intravenous trastuzumab.

In terms of efficacy, the subcutaneous product demonstrated noninferior plasma levels of pertuzumab, which was the primary endpoint, when compared with IV administration of pertuzumab.

Safety was comparable between the two approaches, with no new safety signals using the subcutaneous delivery method, including no “meaningful difference” in cardiac toxicity, according to Genentech. However, there were more administration-related reactions with the new product. The most common adverse events in both groups were alopecia, nausea, diarrhea, and anemia.

The new product uses a drug delivery technology (Enhanze, Halozyme Therapeutics) that employs a proprietary enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to facilitate the dispersion and absorption of injected therapeutic drugs, according to Genentech.

In May, at the European Society for Medical Oncology Breast Cancer Virtual Meeting 2020, investigators of the phase 2 PHranceSCa study reported that “more than 80%” of patients preferred subcutaneous to intravenous administration of pertuzumab and trastuzumab.

This article first appeared on Medscape.com.

CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.

“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.

The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.

Not everyone was as successful.

That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”

Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”

ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.

This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.

Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.

At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”

What did oncologists miss most with virtual ASCO?

Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.

Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.

He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”

The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.

Virtual meeting ‘like homework’

George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).

One of his criticisms struck a nerve – that the online meeting was “like homework.”

“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.

Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.

“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.

Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.

What will happen with ASCO next year?

Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.

“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”

Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”

Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”

Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”

Others were uncertain.

Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”

Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.

“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.

A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.

Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”

Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”

City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
 

“This year was special”

On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.

He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”

Other oncologists praised the accessibility of the virtual meeting.

“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.

“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that  “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”

ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”

With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.

CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.

“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.

The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.

Not everyone was as successful.

That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”

Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”

ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.

This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.

Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.

At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”

What did oncologists miss most with virtual ASCO?

Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.

Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.

He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”

The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.

Virtual meeting ‘like homework’

George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).

One of his criticisms struck a nerve – that the online meeting was “like homework.”

“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.

Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.

“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.

Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.

What will happen with ASCO next year?

Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.

“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”

Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”

Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”

Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”

Others were uncertain.

Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”

Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.

“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.

A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.

Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”

Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”

City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
 

“This year was special”

On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.

He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”

Other oncologists praised the accessibility of the virtual meeting.

“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.

“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that  “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”

ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”

With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.

CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.

“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.

The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.

Not everyone was as successful.

That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”

Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”

ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.

This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.

Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.

At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”

What did oncologists miss most with virtual ASCO?

Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.

Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.

He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”

The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.

Virtual meeting ‘like homework’

George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).

One of his criticisms struck a nerve – that the online meeting was “like homework.”

“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.

Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.

“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.

Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.

What will happen with ASCO next year?

Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.

“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”

Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”

Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”

Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”

Others were uncertain.

Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”

Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.

“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.

A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.

Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”

Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”

City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
 

“This year was special”

On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.

He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”

Other oncologists praised the accessibility of the virtual meeting.

“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.

“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that  “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”

ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”

With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.

The proton pump inhibitor (PPI) omeprazole may be a useful addition to treatment for triple-negative breast cancer, as it boosted the expected rate of tumor disappearance among women with early-stage disease, according to the results of a phase 2 trial.

The trial results are presented online at the 2020 virtual annual meeting of the American Society of Clinical Oncology.

The rationale behind the approach includes the fact that PPIs inhibit fatty acid synthase (FASN), an enzyme overexpressed in 70% of newly diagnosed triple-negative breast cancers (TNBC) and associated with poor prognosis.

In the study, omeprazole, a generic drug for gastroesophageal reflux, was added to standard chemotherapy. Both were given to 42 women as neoadjuvant treatment in the weeks before breast surgery at five US centers in the single-arm study.

The pathologic complete response (pCR) rate was 71% in the study population, which is higher than the typical 40% seen in patients treated with standard AC-T (adriamycin and cyclophosphamide plus a taxane), said lead author Sagar D. Sardesai, MBBS, a medical oncologist at Ohio State Comprehensive Cancer Center in Columbus.

“It’s exciting,” said Dr. Sardesai in an interview. “Overall, triple-negative patients who achieve a pCR have a very good outcome.”

That complete disappearance of the tumor is a surrogate for overall survival in TNBC, and patients who achieve it have a greatly reduced risk of recurrence or death, he explained.

Natalie Berger, MD, medical oncologist, Icahn School of Medicine at Mount Sinai, New York City, said the study’s pCR rates were “much higher” than expected and “intriguing and hypothesis generating.”

But Dr. Berger, who was not involved in the study, wanted to see more data.

“Having a non-chemotherapeutic agent to offer our patients with TNBC that improves pCR rates without added toxicity would be an exciting finding, but we need a larger randomized study,” she said in an email.

The researchers, who include high-profile breast cancer specialist Kathy Miller, MD, of Indiana University, are seeking a National Cancer Institute or Department of Defense grant to mount a 100-plus patient randomized trial.
 

Potential Drug Target for Some Years

Dr. Sardesai explained that FASN, which is an enzyme, helps generate fatty acids that are a key to cancer cell survival. FASN is primarily found in hormone-dominated tissue such as those of the endometrium, prostate, and breast.

PPIs “selectively inhibit FASN activity and induce apoptosis in breast cancer cell lines with minimal effect on non-malignant cells,” wrote the study authors in their meeting abstract.

The only other known agent known to inhibit FASN is the weight loss drug orlistat, which is poorly absorbed by the body and unlikely to impact cancer cells, Dr. Sardesai said.

FASN has been a potential drug target in TNBC for 10 to 15 years, but the first clinical evidence of efficacy in solid tumors was only seen in the last 5 years, he commented.

In 2015, Chinese investigators reported that the PPI esomeprazole in combination with chemotherapy produced a 5-month improvement in progression-free survival (vs. chemo alone) among a subset of 15 TNBC patients in a randomized trial of 94 patients with a variety of breast cancer types.
 

No Added Toxicity, But Some Unexpected Findings

The study was conducted in patients with early-stage, operable TNBC (with and without baseline FASN expression) and no prior PPI use within 12 months.

All patients started daily high-dose omeprazole 4 to 7 days prior to start of AC-T neoadjuvant chemotherapy (the addition of carboplatin was allowed per physician discretion) and continued until surgery.

The primary endpoint was pCR, defined as no residual invasive disease in breast or axilla, in patients with baseline FASN expression (FASN+). The pCR rate was 71.4% in the 28 FASN+ patients and 71.8% in all 42 enrolled patients. The researchers had targeted a pCR rate of 60% in the FASN+ patients. Also, among the subset of 15 patients who received carboplatin with AC-T, the pCR was 73%.

These two findings both have limitations, commented Dr. Berger. She pointed out that it is “unexplained” as to why the pCR rates were similar among the FASN+ patients and the total population (including 14 FASN– patients); the pCR rate would be expected to be lower in the total population, she suggested.

Further, it was also unexplained as to why there were similar pCR rates with or without carboplatin; other research has demonstrated improved pCR rates in patients receiving additional carboplatin (compared to AC-T alone) but at the cost of increased toxicity, she said.

Dr. Sardesai said that omeprazole was well tolerated with no known grade 3 or 4 toxicities and that the chemotherapy toxicity was similar to prior studies of AC-T. PPIs have side effects if taken for longer than a year, including a higher risk of infections, osteoporosis, and low magnesium, he also commented.

“Omeprazole can be safely administered in doses that inhibit FASN. The addition of high-dose omeprazole to neoadjuvant AC-T yields a promising pCR rate without adding toxicity,” the authors concluded in their abstract.

Dr. Sardesai also highlighted the fact that using a PPI for breast cancer is an example of drug repurposing. The approach offers a way of rapid drug development because PPIs have complete safety and pharmacokinetics data available, he said. “If we can prove the efficacy, the treatment can move forward quickly and be available in clinical practice much sooner than with traditional drug development.”

The study was funded by the Breast Cancer Research Foundation. Dr. Sardesai disclosed financial ties to Novartis and Immunomedics. Other study authors have ties to industry. Dr. Berger disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The proton pump inhibitor (PPI) omeprazole may be a useful addition to treatment for triple-negative breast cancer, as it boosted the expected rate of tumor disappearance among women with early-stage disease, according to the results of a phase 2 trial.

The trial results are presented online at the 2020 virtual annual meeting of the American Society of Clinical Oncology.

The rationale behind the approach includes the fact that PPIs inhibit fatty acid synthase (FASN), an enzyme overexpressed in 70% of newly diagnosed triple-negative breast cancers (TNBC) and associated with poor prognosis.

In the study, omeprazole, a generic drug for gastroesophageal reflux, was added to standard chemotherapy. Both were given to 42 women as neoadjuvant treatment in the weeks before breast surgery at five US centers in the single-arm study.

The pathologic complete response (pCR) rate was 71% in the study population, which is higher than the typical 40% seen in patients treated with standard AC-T (adriamycin and cyclophosphamide plus a taxane), said lead author Sagar D. Sardesai, MBBS, a medical oncologist at Ohio State Comprehensive Cancer Center in Columbus.

“It’s exciting,” said Dr. Sardesai in an interview. “Overall, triple-negative patients who achieve a pCR have a very good outcome.”

That complete disappearance of the tumor is a surrogate for overall survival in TNBC, and patients who achieve it have a greatly reduced risk of recurrence or death, he explained.

Natalie Berger, MD, medical oncologist, Icahn School of Medicine at Mount Sinai, New York City, said the study’s pCR rates were “much higher” than expected and “intriguing and hypothesis generating.”

But Dr. Berger, who was not involved in the study, wanted to see more data.

“Having a non-chemotherapeutic agent to offer our patients with TNBC that improves pCR rates without added toxicity would be an exciting finding, but we need a larger randomized study,” she said in an email.

The researchers, who include high-profile breast cancer specialist Kathy Miller, MD, of Indiana University, are seeking a National Cancer Institute or Department of Defense grant to mount a 100-plus patient randomized trial.
 

Potential Drug Target for Some Years

Dr. Sardesai explained that FASN, which is an enzyme, helps generate fatty acids that are a key to cancer cell survival. FASN is primarily found in hormone-dominated tissue such as those of the endometrium, prostate, and breast.

PPIs “selectively inhibit FASN activity and induce apoptosis in breast cancer cell lines with minimal effect on non-malignant cells,” wrote the study authors in their meeting abstract.

The only other known agent known to inhibit FASN is the weight loss drug orlistat, which is poorly absorbed by the body and unlikely to impact cancer cells, Dr. Sardesai said.

FASN has been a potential drug target in TNBC for 10 to 15 years, but the first clinical evidence of efficacy in solid tumors was only seen in the last 5 years, he commented.

In 2015, Chinese investigators reported that the PPI esomeprazole in combination with chemotherapy produced a 5-month improvement in progression-free survival (vs. chemo alone) among a subset of 15 TNBC patients in a randomized trial of 94 patients with a variety of breast cancer types.
 

No Added Toxicity, But Some Unexpected Findings

The study was conducted in patients with early-stage, operable TNBC (with and without baseline FASN expression) and no prior PPI use within 12 months.

All patients started daily high-dose omeprazole 4 to 7 days prior to start of AC-T neoadjuvant chemotherapy (the addition of carboplatin was allowed per physician discretion) and continued until surgery.

The primary endpoint was pCR, defined as no residual invasive disease in breast or axilla, in patients with baseline FASN expression (FASN+). The pCR rate was 71.4% in the 28 FASN+ patients and 71.8% in all 42 enrolled patients. The researchers had targeted a pCR rate of 60% in the FASN+ patients. Also, among the subset of 15 patients who received carboplatin with AC-T, the pCR was 73%.

These two findings both have limitations, commented Dr. Berger. She pointed out that it is “unexplained” as to why the pCR rates were similar among the FASN+ patients and the total population (including 14 FASN– patients); the pCR rate would be expected to be lower in the total population, she suggested.

Further, it was also unexplained as to why there were similar pCR rates with or without carboplatin; other research has demonstrated improved pCR rates in patients receiving additional carboplatin (compared to AC-T alone) but at the cost of increased toxicity, she said.

Dr. Sardesai said that omeprazole was well tolerated with no known grade 3 or 4 toxicities and that the chemotherapy toxicity was similar to prior studies of AC-T. PPIs have side effects if taken for longer than a year, including a higher risk of infections, osteoporosis, and low magnesium, he also commented.

“Omeprazole can be safely administered in doses that inhibit FASN. The addition of high-dose omeprazole to neoadjuvant AC-T yields a promising pCR rate without adding toxicity,” the authors concluded in their abstract.

Dr. Sardesai also highlighted the fact that using a PPI for breast cancer is an example of drug repurposing. The approach offers a way of rapid drug development because PPIs have complete safety and pharmacokinetics data available, he said. “If we can prove the efficacy, the treatment can move forward quickly and be available in clinical practice much sooner than with traditional drug development.”

The study was funded by the Breast Cancer Research Foundation. Dr. Sardesai disclosed financial ties to Novartis and Immunomedics. Other study authors have ties to industry. Dr. Berger disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The proton pump inhibitor (PPI) omeprazole may be a useful addition to treatment for triple-negative breast cancer, as it boosted the expected rate of tumor disappearance among women with early-stage disease, according to the results of a phase 2 trial.

The trial results are presented online at the 2020 virtual annual meeting of the American Society of Clinical Oncology.

The rationale behind the approach includes the fact that PPIs inhibit fatty acid synthase (FASN), an enzyme overexpressed in 70% of newly diagnosed triple-negative breast cancers (TNBC) and associated with poor prognosis.

In the study, omeprazole, a generic drug for gastroesophageal reflux, was added to standard chemotherapy. Both were given to 42 women as neoadjuvant treatment in the weeks before breast surgery at five US centers in the single-arm study.

The pathologic complete response (pCR) rate was 71% in the study population, which is higher than the typical 40% seen in patients treated with standard AC-T (adriamycin and cyclophosphamide plus a taxane), said lead author Sagar D. Sardesai, MBBS, a medical oncologist at Ohio State Comprehensive Cancer Center in Columbus.

“It’s exciting,” said Dr. Sardesai in an interview. “Overall, triple-negative patients who achieve a pCR have a very good outcome.”

That complete disappearance of the tumor is a surrogate for overall survival in TNBC, and patients who achieve it have a greatly reduced risk of recurrence or death, he explained.

Natalie Berger, MD, medical oncologist, Icahn School of Medicine at Mount Sinai, New York City, said the study’s pCR rates were “much higher” than expected and “intriguing and hypothesis generating.”

But Dr. Berger, who was not involved in the study, wanted to see more data.

“Having a non-chemotherapeutic agent to offer our patients with TNBC that improves pCR rates without added toxicity would be an exciting finding, but we need a larger randomized study,” she said in an email.

The researchers, who include high-profile breast cancer specialist Kathy Miller, MD, of Indiana University, are seeking a National Cancer Institute or Department of Defense grant to mount a 100-plus patient randomized trial.
 

Potential Drug Target for Some Years

Dr. Sardesai explained that FASN, which is an enzyme, helps generate fatty acids that are a key to cancer cell survival. FASN is primarily found in hormone-dominated tissue such as those of the endometrium, prostate, and breast.

PPIs “selectively inhibit FASN activity and induce apoptosis in breast cancer cell lines with minimal effect on non-malignant cells,” wrote the study authors in their meeting abstract.

The only other known agent known to inhibit FASN is the weight loss drug orlistat, which is poorly absorbed by the body and unlikely to impact cancer cells, Dr. Sardesai said.

FASN has been a potential drug target in TNBC for 10 to 15 years, but the first clinical evidence of efficacy in solid tumors was only seen in the last 5 years, he commented.

In 2015, Chinese investigators reported that the PPI esomeprazole in combination with chemotherapy produced a 5-month improvement in progression-free survival (vs. chemo alone) among a subset of 15 TNBC patients in a randomized trial of 94 patients with a variety of breast cancer types.
 

No Added Toxicity, But Some Unexpected Findings

The study was conducted in patients with early-stage, operable TNBC (with and without baseline FASN expression) and no prior PPI use within 12 months.

All patients started daily high-dose omeprazole 4 to 7 days prior to start of AC-T neoadjuvant chemotherapy (the addition of carboplatin was allowed per physician discretion) and continued until surgery.

The primary endpoint was pCR, defined as no residual invasive disease in breast or axilla, in patients with baseline FASN expression (FASN+). The pCR rate was 71.4% in the 28 FASN+ patients and 71.8% in all 42 enrolled patients. The researchers had targeted a pCR rate of 60% in the FASN+ patients. Also, among the subset of 15 patients who received carboplatin with AC-T, the pCR was 73%.

These two findings both have limitations, commented Dr. Berger. She pointed out that it is “unexplained” as to why the pCR rates were similar among the FASN+ patients and the total population (including 14 FASN– patients); the pCR rate would be expected to be lower in the total population, she suggested.

Further, it was also unexplained as to why there were similar pCR rates with or without carboplatin; other research has demonstrated improved pCR rates in patients receiving additional carboplatin (compared to AC-T alone) but at the cost of increased toxicity, she said.

Dr. Sardesai said that omeprazole was well tolerated with no known grade 3 or 4 toxicities and that the chemotherapy toxicity was similar to prior studies of AC-T. PPIs have side effects if taken for longer than a year, including a higher risk of infections, osteoporosis, and low magnesium, he also commented.

“Omeprazole can be safely administered in doses that inhibit FASN. The addition of high-dose omeprazole to neoadjuvant AC-T yields a promising pCR rate without adding toxicity,” the authors concluded in their abstract.

Dr. Sardesai also highlighted the fact that using a PPI for breast cancer is an example of drug repurposing. The approach offers a way of rapid drug development because PPIs have complete safety and pharmacokinetics data available, he said. “If we can prove the efficacy, the treatment can move forward quickly and be available in clinical practice much sooner than with traditional drug development.”

The study was funded by the Breast Cancer Research Foundation. Dr. Sardesai disclosed financial ties to Novartis and Immunomedics. Other study authors have ties to industry. Dr. Berger disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Is maintenance therapy with an immune checkpoint inhibitor a good idea for patients with advanced bladder cancer who do not progress after initial chemotherapy?

Yes, and furthermore this approach offers “a new first-line standard of care for advanced urothelial cancer,” said Thomas Powles, MD, professor of genitourinary oncology and director of the Barts Cancer Centre in London.

Dr. Powles was discussing “first-line maintenance therapy” with avelumab (Bavencio, EMD Serono and Pfizer) from the JAVELIN Bladder 100 trial.

Results from this trial will be presented at the plenary session of the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because the coronavirus pandemic. ASCO chief medical officer Richard Schilsky, MD, PhD, highlighted this abstract as one of three from the plenary session that were “practice changing.”

Dr. Powles provided a glimpse of the results at a premeeting press briefing.

The trial involved 700 patients who had not progressed after at least four cycles of first-line, platinum-based chemotherapy. Maintenance therapy with avelumab improved overall survival by 7.1 months when compared with best supportive care (BSC) alone.

The median OS was 21.4 months for avelumab plus BSC versus 14.3 months for BSC alone (hazard ratio, 0.69; P = .0005).

An expert not involved with the study was impressed with the outcome.

“The data are encouraging and we look forward to FDA review, and hopefully approval [in this setting],” said Padmanee Sharma, MD, PhD, a genitourinary medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.

Avelumab is already approved for use in advanced urothelial cancer, but in a second-line setting, like a number of other immune checkpoint inhibitors.
 

“Instead of waiting for cancer to return”

Dr. Powles commented that about 65%-75% of patients with advanced urothelial cancer have disease control with first-line chemotherapy, but that progression-free survival (PFS) and OS are “short” because of chemoresistance.

Many patients do not receive second-line treatment with immunotherapy and only a “minority” achieve durable clinical benefit, he added.

“Instead of waiting for the cancer to return,” which it will do “quickly,” Dr. Powles suggested that maintenance with immunotherapy should become the standard of care.

“Our findings should give hope to many patients with advanced urothelial cancer who face a very challenging and difficult condition,” coauthor Petros Grivas, MD, PhD, clinical director of the Genitourinary Cancers Program at the Seattle Cancer Care Alliance, said in a statement. He was the global coprincipal investigator of the JAVELIN Bladder 100 trial.

“People with advanced urothelial cancer generally have a poor prognosis, and most experience cancer progression (growth) within 8 months after initiation of first-line chemotherapy,” he said.

“We are very excited with these results, which indicate that immunotherapy with avelumab first-line maintenance could offer a new treatment option that helps patients live longer. Even if this is likely not a complete cure and may cause potential side effects in some patients, the significant prolongation of overall survival is clearly a remarkable improvement, while many treated patients may not experience significant side effects from this approach,” he added.

The safety profile was “manageable” and consistent with other studies of avelumab, Dr. Powles reported.

All-causality adverse events (AEs) were reported at any grade in 98% versus 77.7% in the avelumab plus BSC versus BSC-alone groups; AEs of grade 3 or higher were 47.4% vs 25.2%. The most frequent grade ≥3 AEs were urinary tract infection (4.4% vs. 2.6%), anemia (3.8% vs. 2.9%), hematuria (1.7% vs. 1.4%), fatigue (1.7% vs. 0.6%), and back pain (1.2% vs. 2.3%).

The results from JAVELIN with avelumab show the “largest survival benefit” seen so far in advanced urothelial cancer in the maintenance setting, according to ASCO press materials.

Has there ever been a survival benefit found with maintenance therapy?

No, according to a 2019 review in Future Oncology. Three prospective, randomized, controlled trials (of vinflunine, sunitinib, and lapatinib, respectively) did not reveal any significant oncologic benefit vs placebo.

But in a phase 2, randomized, controlled trial involving 107 patients, maintenance pembrolizumab provided longer PFS, compared with placebo (5.4 vs 3.2 months, HR, 0.64; 95% confidence interval, 0.41-0.98).

This pembrolizumab trial showed a “similar PFS hazard ratio” to that seen with avelumab in JAVELIN, Dr. Powles commented, noting however that the pembrolizumab trial was not designed to look at survival.
 

Even better response among PD-L1-positive patients

JAVELIN patients had unresectable locally advanced or metastatic urothelial carcinoma and were treated with gemcitabine with either cisplatin or carboplatin.

Just over half (51%) of these patients had tumors that were PD-L1 positive.

The maintenance therapy strategy was even more effective in these patients. Avelumab plus BSC significantly prolonged OS versus BSC alone in patients with PD-L1-positive tumors (HR, 0.56; 1-sided P = .0003). Median OS was not reached versus 17.1 months, respectively.

An OS benefit was also observed across all prespecified subgroups, including those patients with visceral metastases.

Commenting on the study, Dr. Sharma said she would like to see more detailed outcome data related to the number of chemotherapy cycles administered (the range was 4 to 6) and information on the amount of time between the end of chemo to the start of avelumab. Dr. Powles commented that his international team has not looked at number of cycles and outcome, nor the time from completion of chemotherapy and randomization. “They are both valid questions for the future,” he said.

The study was funded by Pfizer. Dr. Powles and many of the coauthors have financial relationships with Pfizer and other pharmaceuticals. Dr. Sharma has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Is maintenance therapy with an immune checkpoint inhibitor a good idea for patients with advanced bladder cancer who do not progress after initial chemotherapy?

Yes, and furthermore this approach offers “a new first-line standard of care for advanced urothelial cancer,” said Thomas Powles, MD, professor of genitourinary oncology and director of the Barts Cancer Centre in London.

Dr. Powles was discussing “first-line maintenance therapy” with avelumab (Bavencio, EMD Serono and Pfizer) from the JAVELIN Bladder 100 trial.

Results from this trial will be presented at the plenary session of the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because the coronavirus pandemic. ASCO chief medical officer Richard Schilsky, MD, PhD, highlighted this abstract as one of three from the plenary session that were “practice changing.”

Dr. Powles provided a glimpse of the results at a premeeting press briefing.

The trial involved 700 patients who had not progressed after at least four cycles of first-line, platinum-based chemotherapy. Maintenance therapy with avelumab improved overall survival by 7.1 months when compared with best supportive care (BSC) alone.

The median OS was 21.4 months for avelumab plus BSC versus 14.3 months for BSC alone (hazard ratio, 0.69; P = .0005).

An expert not involved with the study was impressed with the outcome.

“The data are encouraging and we look forward to FDA review, and hopefully approval [in this setting],” said Padmanee Sharma, MD, PhD, a genitourinary medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.

Avelumab is already approved for use in advanced urothelial cancer, but in a second-line setting, like a number of other immune checkpoint inhibitors.
 

“Instead of waiting for cancer to return”

Dr. Powles commented that about 65%-75% of patients with advanced urothelial cancer have disease control with first-line chemotherapy, but that progression-free survival (PFS) and OS are “short” because of chemoresistance.

Many patients do not receive second-line treatment with immunotherapy and only a “minority” achieve durable clinical benefit, he added.

“Instead of waiting for the cancer to return,” which it will do “quickly,” Dr. Powles suggested that maintenance with immunotherapy should become the standard of care.

“Our findings should give hope to many patients with advanced urothelial cancer who face a very challenging and difficult condition,” coauthor Petros Grivas, MD, PhD, clinical director of the Genitourinary Cancers Program at the Seattle Cancer Care Alliance, said in a statement. He was the global coprincipal investigator of the JAVELIN Bladder 100 trial.

“People with advanced urothelial cancer generally have a poor prognosis, and most experience cancer progression (growth) within 8 months after initiation of first-line chemotherapy,” he said.

“We are very excited with these results, which indicate that immunotherapy with avelumab first-line maintenance could offer a new treatment option that helps patients live longer. Even if this is likely not a complete cure and may cause potential side effects in some patients, the significant prolongation of overall survival is clearly a remarkable improvement, while many treated patients may not experience significant side effects from this approach,” he added.

The safety profile was “manageable” and consistent with other studies of avelumab, Dr. Powles reported.

All-causality adverse events (AEs) were reported at any grade in 98% versus 77.7% in the avelumab plus BSC versus BSC-alone groups; AEs of grade 3 or higher were 47.4% vs 25.2%. The most frequent grade ≥3 AEs were urinary tract infection (4.4% vs. 2.6%), anemia (3.8% vs. 2.9%), hematuria (1.7% vs. 1.4%), fatigue (1.7% vs. 0.6%), and back pain (1.2% vs. 2.3%).

The results from JAVELIN with avelumab show the “largest survival benefit” seen so far in advanced urothelial cancer in the maintenance setting, according to ASCO press materials.

Has there ever been a survival benefit found with maintenance therapy?

No, according to a 2019 review in Future Oncology. Three prospective, randomized, controlled trials (of vinflunine, sunitinib, and lapatinib, respectively) did not reveal any significant oncologic benefit vs placebo.

But in a phase 2, randomized, controlled trial involving 107 patients, maintenance pembrolizumab provided longer PFS, compared with placebo (5.4 vs 3.2 months, HR, 0.64; 95% confidence interval, 0.41-0.98).

This pembrolizumab trial showed a “similar PFS hazard ratio” to that seen with avelumab in JAVELIN, Dr. Powles commented, noting however that the pembrolizumab trial was not designed to look at survival.
 

Even better response among PD-L1-positive patients

JAVELIN patients had unresectable locally advanced or metastatic urothelial carcinoma and were treated with gemcitabine with either cisplatin or carboplatin.

Just over half (51%) of these patients had tumors that were PD-L1 positive.

The maintenance therapy strategy was even more effective in these patients. Avelumab plus BSC significantly prolonged OS versus BSC alone in patients with PD-L1-positive tumors (HR, 0.56; 1-sided P = .0003). Median OS was not reached versus 17.1 months, respectively.

An OS benefit was also observed across all prespecified subgroups, including those patients with visceral metastases.

Commenting on the study, Dr. Sharma said she would like to see more detailed outcome data related to the number of chemotherapy cycles administered (the range was 4 to 6) and information on the amount of time between the end of chemo to the start of avelumab. Dr. Powles commented that his international team has not looked at number of cycles and outcome, nor the time from completion of chemotherapy and randomization. “They are both valid questions for the future,” he said.

The study was funded by Pfizer. Dr. Powles and many of the coauthors have financial relationships with Pfizer and other pharmaceuticals. Dr. Sharma has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Is maintenance therapy with an immune checkpoint inhibitor a good idea for patients with advanced bladder cancer who do not progress after initial chemotherapy?

Yes, and furthermore this approach offers “a new first-line standard of care for advanced urothelial cancer,” said Thomas Powles, MD, professor of genitourinary oncology and director of the Barts Cancer Centre in London.

Dr. Powles was discussing “first-line maintenance therapy” with avelumab (Bavencio, EMD Serono and Pfizer) from the JAVELIN Bladder 100 trial.

Results from this trial will be presented at the plenary session of the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because the coronavirus pandemic. ASCO chief medical officer Richard Schilsky, MD, PhD, highlighted this abstract as one of three from the plenary session that were “practice changing.”

Dr. Powles provided a glimpse of the results at a premeeting press briefing.

The trial involved 700 patients who had not progressed after at least four cycles of first-line, platinum-based chemotherapy. Maintenance therapy with avelumab improved overall survival by 7.1 months when compared with best supportive care (BSC) alone.

The median OS was 21.4 months for avelumab plus BSC versus 14.3 months for BSC alone (hazard ratio, 0.69; P = .0005).

An expert not involved with the study was impressed with the outcome.

“The data are encouraging and we look forward to FDA review, and hopefully approval [in this setting],” said Padmanee Sharma, MD, PhD, a genitourinary medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.

Avelumab is already approved for use in advanced urothelial cancer, but in a second-line setting, like a number of other immune checkpoint inhibitors.
 

“Instead of waiting for cancer to return”

Dr. Powles commented that about 65%-75% of patients with advanced urothelial cancer have disease control with first-line chemotherapy, but that progression-free survival (PFS) and OS are “short” because of chemoresistance.

Many patients do not receive second-line treatment with immunotherapy and only a “minority” achieve durable clinical benefit, he added.

“Instead of waiting for the cancer to return,” which it will do “quickly,” Dr. Powles suggested that maintenance with immunotherapy should become the standard of care.

“Our findings should give hope to many patients with advanced urothelial cancer who face a very challenging and difficult condition,” coauthor Petros Grivas, MD, PhD, clinical director of the Genitourinary Cancers Program at the Seattle Cancer Care Alliance, said in a statement. He was the global coprincipal investigator of the JAVELIN Bladder 100 trial.

“People with advanced urothelial cancer generally have a poor prognosis, and most experience cancer progression (growth) within 8 months after initiation of first-line chemotherapy,” he said.

“We are very excited with these results, which indicate that immunotherapy with avelumab first-line maintenance could offer a new treatment option that helps patients live longer. Even if this is likely not a complete cure and may cause potential side effects in some patients, the significant prolongation of overall survival is clearly a remarkable improvement, while many treated patients may not experience significant side effects from this approach,” he added.

The safety profile was “manageable” and consistent with other studies of avelumab, Dr. Powles reported.

All-causality adverse events (AEs) were reported at any grade in 98% versus 77.7% in the avelumab plus BSC versus BSC-alone groups; AEs of grade 3 or higher were 47.4% vs 25.2%. The most frequent grade ≥3 AEs were urinary tract infection (4.4% vs. 2.6%), anemia (3.8% vs. 2.9%), hematuria (1.7% vs. 1.4%), fatigue (1.7% vs. 0.6%), and back pain (1.2% vs. 2.3%).

The results from JAVELIN with avelumab show the “largest survival benefit” seen so far in advanced urothelial cancer in the maintenance setting, according to ASCO press materials.

Has there ever been a survival benefit found with maintenance therapy?

No, according to a 2019 review in Future Oncology. Three prospective, randomized, controlled trials (of vinflunine, sunitinib, and lapatinib, respectively) did not reveal any significant oncologic benefit vs placebo.

But in a phase 2, randomized, controlled trial involving 107 patients, maintenance pembrolizumab provided longer PFS, compared with placebo (5.4 vs 3.2 months, HR, 0.64; 95% confidence interval, 0.41-0.98).

This pembrolizumab trial showed a “similar PFS hazard ratio” to that seen with avelumab in JAVELIN, Dr. Powles commented, noting however that the pembrolizumab trial was not designed to look at survival.
 

Even better response among PD-L1-positive patients

JAVELIN patients had unresectable locally advanced or metastatic urothelial carcinoma and were treated with gemcitabine with either cisplatin or carboplatin.

Just over half (51%) of these patients had tumors that were PD-L1 positive.

The maintenance therapy strategy was even more effective in these patients. Avelumab plus BSC significantly prolonged OS versus BSC alone in patients with PD-L1-positive tumors (HR, 0.56; 1-sided P = .0003). Median OS was not reached versus 17.1 months, respectively.

An OS benefit was also observed across all prespecified subgroups, including those patients with visceral metastases.

Commenting on the study, Dr. Sharma said she would like to see more detailed outcome data related to the number of chemotherapy cycles administered (the range was 4 to 6) and information on the amount of time between the end of chemo to the start of avelumab. Dr. Powles commented that his international team has not looked at number of cycles and outcome, nor the time from completion of chemotherapy and randomization. “They are both valid questions for the future,” he said.

The study was funded by Pfizer. Dr. Powles and many of the coauthors have financial relationships with Pfizer and other pharmaceuticals. Dr. Sharma has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

The incidence of advanced prostate cancers in the United States “persistently” increased annually for 5 years after the United States Preventive Services Task Force (USPSTF) controversially advised in 2012 against prostate-specific antigen (PSA) screening in men of all ages, new research indicates.

But a biostatistician not involved with the study said the USPSTF’s recommendation is not wholly to blame because “you need 5 to 7 years of lag time at a minimum to influence PSA screening,” and suggested that other factors were at play.

In the new study, Ahmedin Jemal, DVM, PhD, of the American Cancer Society, and colleagues report that for the period 2012­–2016 there were yearly statistically significant upticks in the incidence of regional-stage disease (by an absolute 11% per year) and in distant-stage disease (by an absolute 5% per year).

At the same time, there were annual drops in the incidence of localized prostate cancers in men 50 years or older.

The new study is the first to report data out to the end of 2016.

The two trends — the increase in advanced cancers and decrease in early-stage cancers — have been occurring for 10 years, more or less, but with a steady, sharp rise in advanced disease starting in 2010 to 2012, the findings show.

“These data illustrate the trade-off between higher screening rates and more early-stage disease diagnoses (possibly overdiagnosis and overtreatment) and lower screening rates and more late-stage (possibly fatal) disease,” the authors comment.

The study was published online May 20 in the Journal of the National Cancer Institute.

Several previous studies have reported incidence pattern changes following the USPSTF recommendations against PSA screening for men aged 75 or older in 2008 and all men in 2012, but the data went no further than 2015.

“We saw hints of these changes in the past few years and now we have further confirmation,” said Ahmad Shabsigh, MD, urologic oncologist at the Ohio State University Comprehensive Cancer Center, who was asked for independent comment.

“What is a surprise is that it’s every year,” Shabsigh told Medscape Medical News, referring to the advanced cancer incidence increases.

“To see it so clearly in this study is sad,” Shabsigh added.

The study period started in 2005, but did not cover the years after 2018, when USPSTF recommendations changed again and advised that screening be “individualized” for men 55 to 69, and that men 70 and over should be excluded.

US cancer registry data, which are the source of the current study, are not yet available to assess the impact of this most recent change.

End in sight?

There has been a decline in the proportion of men undergoing PSA tests in the US in recent years, the study authors point out.

Routine PSA testing rates among men aged 50 and older declined from 40.6% in 2008 to 38.3% in 2010, and dropped to 31.5% in 2013, a percentage which held again in 2015, per national self-reported survey data.

The study authors say the cause of the rise in advanced cancers is uncertain because of the descriptive nature of their research.

But Andrew Vickers, PhD, a biostatistician at the Memorial Sloan Kettering Cancer Center in New York City, said the rise in advanced cancers and the drop in early-stage cancers reported in the study are “suggestive of a causal relationship” and a “screening effect.”

Vickers argues that there were “a whole bunch of trends that came together in the late [2000s] to influence [PSA] screening.”

For example, two landmark randomized clinical trials of PSA screening first reported “unfavorable” results in 2009, which is during the period covered in the current study, and dampened enthusiasm for screening.

The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial reported little or no effect on mortality, the primary outcome of the trials.

• First, physicians need to get consent for all PSA tests.
• Second, PSA tests should not be administered to older men “who won’t benefit,” such as men 75 years and older with comorbidities such as heart disease.
• Third, PSA testing should be restricted to younger men.
• Fourth, clinicians need to be more restrictive about biopsy. “It used to be if you had a high PSA, you would get a biopsy,” he said, adding that this approach yielded a lot invasive testing in men with low-grade disease. By using additional tests such as the 4Kscore or Prostate Health Index or MRI, clinicians can limit biopsies to men with greater likelihood of a high-grade cancer. Vickers acknowledged conflict of interest on this point, as he is a patent holder of the 4Kscore.
• Fifth, don’t treat men who are very unlikely to benefit, especially men with Gleason grade 6 disease. Use active surveillance for these men, he said. “Using our existing knowledge, I believe we can completely transform the harm-to-benefit ratio of PSA screening. We would drastically reduce overdiagnosis and overtreatment,” he stated.

Additionally, Vickers believes that urologists need to educate local internists and general practitioners and acknowledge that screening and subsequent treatment were “done wrong for a long time.” At the same time, urologists should make it clear that patients will not be biopsied “unless there is a really good reason to believe that they have a high risk of high-grade disease.”

Vickers concluded: “We can reduce the harm and maintain the benefit of screening.”

The study was supported by the American Cancer Society. Jemal and Shabsigh have disclosed no relevant financial relationships. Vickers declared that he is a patent holder of the 4Kscore.

This article first appeared on Medscape.com.

The incidence of advanced prostate cancers in the United States “persistently” increased annually for 5 years after the United States Preventive Services Task Force (USPSTF) controversially advised in 2012 against prostate-specific antigen (PSA) screening in men of all ages, new research indicates.

But a biostatistician not involved with the study said the USPSTF’s recommendation is not wholly to blame because “you need 5 to 7 years of lag time at a minimum to influence PSA screening,” and suggested that other factors were at play.

In the new study, Ahmedin Jemal, DVM, PhD, of the American Cancer Society, and colleagues report that for the period 2012­–2016 there were yearly statistically significant upticks in the incidence of regional-stage disease (by an absolute 11% per year) and in distant-stage disease (by an absolute 5% per year).

At the same time, there were annual drops in the incidence of localized prostate cancers in men 50 years or older.

The new study is the first to report data out to the end of 2016.

The two trends — the increase in advanced cancers and decrease in early-stage cancers — have been occurring for 10 years, more or less, but with a steady, sharp rise in advanced disease starting in 2010 to 2012, the findings show.

“These data illustrate the trade-off between higher screening rates and more early-stage disease diagnoses (possibly overdiagnosis and overtreatment) and lower screening rates and more late-stage (possibly fatal) disease,” the authors comment.

The study was published online May 20 in the Journal of the National Cancer Institute.

Several previous studies have reported incidence pattern changes following the USPSTF recommendations against PSA screening for men aged 75 or older in 2008 and all men in 2012, but the data went no further than 2015.

“We saw hints of these changes in the past few years and now we have further confirmation,” said Ahmad Shabsigh, MD, urologic oncologist at the Ohio State University Comprehensive Cancer Center, who was asked for independent comment.

“What is a surprise is that it’s every year,” Shabsigh told Medscape Medical News, referring to the advanced cancer incidence increases.

“To see it so clearly in this study is sad,” Shabsigh added.

The study period started in 2005, but did not cover the years after 2018, when USPSTF recommendations changed again and advised that screening be “individualized” for men 55 to 69, and that men 70 and over should be excluded.

US cancer registry data, which are the source of the current study, are not yet available to assess the impact of this most recent change.

End in sight?

There has been a decline in the proportion of men undergoing PSA tests in the US in recent years, the study authors point out.

Routine PSA testing rates among men aged 50 and older declined from 40.6% in 2008 to 38.3% in 2010, and dropped to 31.5% in 2013, a percentage which held again in 2015, per national self-reported survey data.

The study authors say the cause of the rise in advanced cancers is uncertain because of the descriptive nature of their research.

But Andrew Vickers, PhD, a biostatistician at the Memorial Sloan Kettering Cancer Center in New York City, said the rise in advanced cancers and the drop in early-stage cancers reported in the study are “suggestive of a causal relationship” and a “screening effect.”

Vickers argues that there were “a whole bunch of trends that came together in the late [2000s] to influence [PSA] screening.”

For example, two landmark randomized clinical trials of PSA screening first reported “unfavorable” results in 2009, which is during the period covered in the current study, and dampened enthusiasm for screening.

The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial reported little or no effect on mortality, the primary outcome of the trials.

• First, physicians need to get consent for all PSA tests.
• Second, PSA tests should not be administered to older men “who won’t benefit,” such as men 75 years and older with comorbidities such as heart disease.
• Third, PSA testing should be restricted to younger men.
• Fourth, clinicians need to be more restrictive about biopsy. “It used to be if you had a high PSA, you would get a biopsy,” he said, adding that this approach yielded a lot invasive testing in men with low-grade disease. By using additional tests such as the 4Kscore or Prostate Health Index or MRI, clinicians can limit biopsies to men with greater likelihood of a high-grade cancer. Vickers acknowledged conflict of interest on this point, as he is a patent holder of the 4Kscore.
• Fifth, don’t treat men who are very unlikely to benefit, especially men with Gleason grade 6 disease. Use active surveillance for these men, he said. “Using our existing knowledge, I believe we can completely transform the harm-to-benefit ratio of PSA screening. We would drastically reduce overdiagnosis and overtreatment,” he stated.

Additionally, Vickers believes that urologists need to educate local internists and general practitioners and acknowledge that screening and subsequent treatment were “done wrong for a long time.” At the same time, urologists should make it clear that patients will not be biopsied “unless there is a really good reason to believe that they have a high risk of high-grade disease.”

Vickers concluded: “We can reduce the harm and maintain the benefit of screening.”

The study was supported by the American Cancer Society. Jemal and Shabsigh have disclosed no relevant financial relationships. Vickers declared that he is a patent holder of the 4Kscore.

This article first appeared on Medscape.com.

The incidence of advanced prostate cancers in the United States “persistently” increased annually for 5 years after the United States Preventive Services Task Force (USPSTF) controversially advised in 2012 against prostate-specific antigen (PSA) screening in men of all ages, new research indicates.

But a biostatistician not involved with the study said the USPSTF’s recommendation is not wholly to blame because “you need 5 to 7 years of lag time at a minimum to influence PSA screening,” and suggested that other factors were at play.

In the new study, Ahmedin Jemal, DVM, PhD, of the American Cancer Society, and colleagues report that for the period 2012­–2016 there were yearly statistically significant upticks in the incidence of regional-stage disease (by an absolute 11% per year) and in distant-stage disease (by an absolute 5% per year).

At the same time, there were annual drops in the incidence of localized prostate cancers in men 50 years or older.

The new study is the first to report data out to the end of 2016.

The two trends — the increase in advanced cancers and decrease in early-stage cancers — have been occurring for 10 years, more or less, but with a steady, sharp rise in advanced disease starting in 2010 to 2012, the findings show.

“These data illustrate the trade-off between higher screening rates and more early-stage disease diagnoses (possibly overdiagnosis and overtreatment) and lower screening rates and more late-stage (possibly fatal) disease,” the authors comment.

The study was published online May 20 in the Journal of the National Cancer Institute.

Several previous studies have reported incidence pattern changes following the USPSTF recommendations against PSA screening for men aged 75 or older in 2008 and all men in 2012, but the data went no further than 2015.

“We saw hints of these changes in the past few years and now we have further confirmation,” said Ahmad Shabsigh, MD, urologic oncologist at the Ohio State University Comprehensive Cancer Center, who was asked for independent comment.

“What is a surprise is that it’s every year,” Shabsigh told Medscape Medical News, referring to the advanced cancer incidence increases.

“To see it so clearly in this study is sad,” Shabsigh added.

The study period started in 2005, but did not cover the years after 2018, when USPSTF recommendations changed again and advised that screening be “individualized” for men 55 to 69, and that men 70 and over should be excluded.

US cancer registry data, which are the source of the current study, are not yet available to assess the impact of this most recent change.

End in sight?

There has been a decline in the proportion of men undergoing PSA tests in the US in recent years, the study authors point out.

Routine PSA testing rates among men aged 50 and older declined from 40.6% in 2008 to 38.3% in 2010, and dropped to 31.5% in 2013, a percentage which held again in 2015, per national self-reported survey data.

The study authors say the cause of the rise in advanced cancers is uncertain because of the descriptive nature of their research.

But Andrew Vickers, PhD, a biostatistician at the Memorial Sloan Kettering Cancer Center in New York City, said the rise in advanced cancers and the drop in early-stage cancers reported in the study are “suggestive of a causal relationship” and a “screening effect.”

Vickers argues that there were “a whole bunch of trends that came together in the late [2000s] to influence [PSA] screening.”

For example, two landmark randomized clinical trials of PSA screening first reported “unfavorable” results in 2009, which is during the period covered in the current study, and dampened enthusiasm for screening.

The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial reported little or no effect on mortality, the primary outcome of the trials.

• First, physicians need to get consent for all PSA tests.
• Second, PSA tests should not be administered to older men “who won’t benefit,” such as men 75 years and older with comorbidities such as heart disease.
• Third, PSA testing should be restricted to younger men.
• Fourth, clinicians need to be more restrictive about biopsy. “It used to be if you had a high PSA, you would get a biopsy,” he said, adding that this approach yielded a lot invasive testing in men with low-grade disease. By using additional tests such as the 4Kscore or Prostate Health Index or MRI, clinicians can limit biopsies to men with greater likelihood of a high-grade cancer. Vickers acknowledged conflict of interest on this point, as he is a patent holder of the 4Kscore.
• Fifth, don’t treat men who are very unlikely to benefit, especially men with Gleason grade 6 disease. Use active surveillance for these men, he said. “Using our existing knowledge, I believe we can completely transform the harm-to-benefit ratio of PSA screening. We would drastically reduce overdiagnosis and overtreatment,” he stated.

Additionally, Vickers believes that urologists need to educate local internists and general practitioners and acknowledge that screening and subsequent treatment were “done wrong for a long time.” At the same time, urologists should make it clear that patients will not be biopsied “unless there is a really good reason to believe that they have a high risk of high-grade disease.”

Vickers concluded: “We can reduce the harm and maintain the benefit of screening.”

The study was supported by the American Cancer Society. Jemal and Shabsigh have disclosed no relevant financial relationships. Vickers declared that he is a patent holder of the 4Kscore.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.