Andrew D. Bowser

For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.

Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.

In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.

“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
 

Utility of CAC scoring in diabetes

This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.

“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.

Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.

“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.

In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
 

CAC scoring and coronary artery stenoses

Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.

The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.

That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.

Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.

“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.

Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.

Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.

They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.

By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.

“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.

Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.

SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.

For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.

Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.

In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.

“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
 

Utility of CAC scoring in diabetes

This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.

“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.

Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.

“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.

In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
 

CAC scoring and coronary artery stenoses

Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.

The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.

That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.

Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.

“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.

Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.

Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.

They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.

By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.

“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.

Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.

SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.

For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.

Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.

In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.

“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
 

Utility of CAC scoring in diabetes

This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.

“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.

Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.

“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.

In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
 

CAC scoring and coronary artery stenoses

Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.

The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.

That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.

Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.

“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.

Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.

Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.

They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.

By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.

“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.

Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.

SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

cardnews@mdedge.com

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

cardnews@mdedge.com

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

cardnews@mdedge.com

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Pembrolizumab treatment significantly improved progression-free survival versus brentuximab vedotin in a randomized, phase 3 trial including patients with relapsed or refractory classical Hodgkin lymphoma, an investigator has reported.

Median progression-free survival (PFS) was 13.2 versus 8.3 months in favor of pembrolizumab, according to the report on the KEYNOTE-204 trial, which included patients with classical Hodgkin lymphoma who either had relapsed after autologous stem cell transplant (SCT) or were ineligible for autologous SCT.

The PFS improvement was “statistically significant and clinically meaningful,” said investigator John Kuruvilla, MD, of Princess Margaret Cancer Centre in Toronto.

“This PFS benefit extended to key subgroups, including those ineligible for autologous transplant, patients with primary refractory disease, and patients who were brentuximab-vedotin naive,” Dr. Kuruvilla added in his presentation, which was part of the American Society of Clinical Oncology virtual scientific program.

Pneumonitis was more frequent in the pembrolizumab arm, but “appeared in general to be quite well managed” among patients who experienced this adverse event, according to Dr. Kuruvilla, who said that treatment with the programmed death–1 inhibitor should be considered “the preferred treatment option and the new standard of care” for patients with relapsed/refractory classic Hodgkin lymphoma who have relapsed after autologous SCT or are ineligible for it.

Although the pneumonitis findings are important to keep in mind, results of KEYNOTE-204 are indeed “practice defining” and immediately impactful, said Mark J. Roschewski, MD, clinical investigator in the lymphoid malignancies branch at the Center for Cancer Research, part of the National Cancer Institute, Bethesda, Md.

“I would select pembrolizumab over brentuximab for this patient population, particularly those that are refractory to chemotherapy,” he said in a commentary on the study also included in the virtual ASCO proceedings.

“There may be specific patient populations that I’d reconsider, such as those that might be at high risk for lung toxicity,” he added. “They may not be suitable for this, but it’s something to at least to be aware of.”

Although the antibody-drug conjugate brentuximab vedotin has been considered the standard of care for patients with relapse after autologous SCT, there has historically been no standard of care for patients who are ineligible for transplant because of chemorefractory disease, advanced age, or comorbidities, Dr. Kuruvilla said in his presentation.

In the KEYNOTE-204 study, 304 patients with relapsed/refractory classic Hodgkin lymphoma were randomized to receive either pembrolizumab 200 mg or brentuximab at 1.8 mg/kg intravenously every 3 weeks for up to 35 cycles.

The median age of patients was 36 years in the pembrolizumab arm and 35 years in the brentuximab vedotin arm, according to the report. Approximately 37% of the patients had previously undergone autologous SCT. About 40% had been refractory to frontline therapy, while 28% relapsed within 12 months of therapy and 32% relapsed later than 12 months.

Median PFS by blinded independent central review was 13.2 versus 8.3 months in the pembrolizumab and brentuximab arms, respectively (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88; P = .00271), Dr. Kuruvilla reported.

The benefit extended to “key subgroups” in the trial, he added, including those who were ineligible for autologous SCT, those with primary refractory disease, and those who were naive to brentuximab vedotin, with HRs of 0.61, 0.52, and 0.67, respectively.

Pembrolizumab was also associated with more durable responses versus brentuximab vedotin, according to the investigator.

The overall response rate was 65.6% and 54.2%, respectively, for pembrolizumab and brentuximab, although this difference of approximately 11 percentage points did not meet criteria for statistical significance, he said. Duration of response was 20.7 months or pembrolizumab and 13.8 months for brentuximab.

The rate of serious treatment-related adverse events was similar between groups, according to Dr. Kuruvilla, who reported grade 3-5 events occurring in 19.6% and 25.0% of the pembrolizumab and brentuximab arms. Serious treatment-related adverse events were numerically more frequent in the pembrolizumab arm (16.2% vs. 10.5%) and there was one treatment-related death caused by pneumonia, seen in the pembrolizumab arm.

Pneumonitis occurred in 2.6% of the brentuximab-treated patients and in 10.8% of pembrolizumab-treated patients, of which half of cases were grade 3-4, according to the report.

In the pembrolizumab arm, pneumonitis was felt to be drug-related in 15 of 16 cases, according to Dr. Kuruvilla, who added that 15 of 16 patients required corticosteroid therapy. “This has led to the resolution of the pneumonitis in 12 of 16 patients, with ongoing resolution in one further patient.”

Research funding for KEYNOTE-204 came from Merck Sharp & Dohme. Dr. Kuruvilla provided disclosures related to Merck and a variety of other pharmaceutical companies. Dr. Roschewski said he had no relationships to disclose.

SOURCE: Kuruvilla J et al. ASCO 2020, Abstract 8005.

Pembrolizumab treatment significantly improved progression-free survival versus brentuximab vedotin in a randomized, phase 3 trial including patients with relapsed or refractory classical Hodgkin lymphoma, an investigator has reported.

Median progression-free survival (PFS) was 13.2 versus 8.3 months in favor of pembrolizumab, according to the report on the KEYNOTE-204 trial, which included patients with classical Hodgkin lymphoma who either had relapsed after autologous stem cell transplant (SCT) or were ineligible for autologous SCT.

The PFS improvement was “statistically significant and clinically meaningful,” said investigator John Kuruvilla, MD, of Princess Margaret Cancer Centre in Toronto.

“This PFS benefit extended to key subgroups, including those ineligible for autologous transplant, patients with primary refractory disease, and patients who were brentuximab-vedotin naive,” Dr. Kuruvilla added in his presentation, which was part of the American Society of Clinical Oncology virtual scientific program.

Pneumonitis was more frequent in the pembrolizumab arm, but “appeared in general to be quite well managed” among patients who experienced this adverse event, according to Dr. Kuruvilla, who said that treatment with the programmed death–1 inhibitor should be considered “the preferred treatment option and the new standard of care” for patients with relapsed/refractory classic Hodgkin lymphoma who have relapsed after autologous SCT or are ineligible for it.

Although the pneumonitis findings are important to keep in mind, results of KEYNOTE-204 are indeed “practice defining” and immediately impactful, said Mark J. Roschewski, MD, clinical investigator in the lymphoid malignancies branch at the Center for Cancer Research, part of the National Cancer Institute, Bethesda, Md.

“I would select pembrolizumab over brentuximab for this patient population, particularly those that are refractory to chemotherapy,” he said in a commentary on the study also included in the virtual ASCO proceedings.

“There may be specific patient populations that I’d reconsider, such as those that might be at high risk for lung toxicity,” he added. “They may not be suitable for this, but it’s something to at least to be aware of.”

Although the antibody-drug conjugate brentuximab vedotin has been considered the standard of care for patients with relapse after autologous SCT, there has historically been no standard of care for patients who are ineligible for transplant because of chemorefractory disease, advanced age, or comorbidities, Dr. Kuruvilla said in his presentation.

In the KEYNOTE-204 study, 304 patients with relapsed/refractory classic Hodgkin lymphoma were randomized to receive either pembrolizumab 200 mg or brentuximab at 1.8 mg/kg intravenously every 3 weeks for up to 35 cycles.

The median age of patients was 36 years in the pembrolizumab arm and 35 years in the brentuximab vedotin arm, according to the report. Approximately 37% of the patients had previously undergone autologous SCT. About 40% had been refractory to frontline therapy, while 28% relapsed within 12 months of therapy and 32% relapsed later than 12 months.

Median PFS by blinded independent central review was 13.2 versus 8.3 months in the pembrolizumab and brentuximab arms, respectively (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88; P = .00271), Dr. Kuruvilla reported.

The benefit extended to “key subgroups” in the trial, he added, including those who were ineligible for autologous SCT, those with primary refractory disease, and those who were naive to brentuximab vedotin, with HRs of 0.61, 0.52, and 0.67, respectively.

Pembrolizumab was also associated with more durable responses versus brentuximab vedotin, according to the investigator.

The overall response rate was 65.6% and 54.2%, respectively, for pembrolizumab and brentuximab, although this difference of approximately 11 percentage points did not meet criteria for statistical significance, he said. Duration of response was 20.7 months or pembrolizumab and 13.8 months for brentuximab.

The rate of serious treatment-related adverse events was similar between groups, according to Dr. Kuruvilla, who reported grade 3-5 events occurring in 19.6% and 25.0% of the pembrolizumab and brentuximab arms. Serious treatment-related adverse events were numerically more frequent in the pembrolizumab arm (16.2% vs. 10.5%) and there was one treatment-related death caused by pneumonia, seen in the pembrolizumab arm.

Pneumonitis occurred in 2.6% of the brentuximab-treated patients and in 10.8% of pembrolizumab-treated patients, of which half of cases were grade 3-4, according to the report.

In the pembrolizumab arm, pneumonitis was felt to be drug-related in 15 of 16 cases, according to Dr. Kuruvilla, who added that 15 of 16 patients required corticosteroid therapy. “This has led to the resolution of the pneumonitis in 12 of 16 patients, with ongoing resolution in one further patient.”

Research funding for KEYNOTE-204 came from Merck Sharp & Dohme. Dr. Kuruvilla provided disclosures related to Merck and a variety of other pharmaceutical companies. Dr. Roschewski said he had no relationships to disclose.

SOURCE: Kuruvilla J et al. ASCO 2020, Abstract 8005.

Pembrolizumab treatment significantly improved progression-free survival versus brentuximab vedotin in a randomized, phase 3 trial including patients with relapsed or refractory classical Hodgkin lymphoma, an investigator has reported.

Median progression-free survival (PFS) was 13.2 versus 8.3 months in favor of pembrolizumab, according to the report on the KEYNOTE-204 trial, which included patients with classical Hodgkin lymphoma who either had relapsed after autologous stem cell transplant (SCT) or were ineligible for autologous SCT.

The PFS improvement was “statistically significant and clinically meaningful,” said investigator John Kuruvilla, MD, of Princess Margaret Cancer Centre in Toronto.

“This PFS benefit extended to key subgroups, including those ineligible for autologous transplant, patients with primary refractory disease, and patients who were brentuximab-vedotin naive,” Dr. Kuruvilla added in his presentation, which was part of the American Society of Clinical Oncology virtual scientific program.

Pneumonitis was more frequent in the pembrolizumab arm, but “appeared in general to be quite well managed” among patients who experienced this adverse event, according to Dr. Kuruvilla, who said that treatment with the programmed death–1 inhibitor should be considered “the preferred treatment option and the new standard of care” for patients with relapsed/refractory classic Hodgkin lymphoma who have relapsed after autologous SCT or are ineligible for it.

Although the pneumonitis findings are important to keep in mind, results of KEYNOTE-204 are indeed “practice defining” and immediately impactful, said Mark J. Roschewski, MD, clinical investigator in the lymphoid malignancies branch at the Center for Cancer Research, part of the National Cancer Institute, Bethesda, Md.

“I would select pembrolizumab over brentuximab for this patient population, particularly those that are refractory to chemotherapy,” he said in a commentary on the study also included in the virtual ASCO proceedings.

“There may be specific patient populations that I’d reconsider, such as those that might be at high risk for lung toxicity,” he added. “They may not be suitable for this, but it’s something to at least to be aware of.”

Although the antibody-drug conjugate brentuximab vedotin has been considered the standard of care for patients with relapse after autologous SCT, there has historically been no standard of care for patients who are ineligible for transplant because of chemorefractory disease, advanced age, or comorbidities, Dr. Kuruvilla said in his presentation.

In the KEYNOTE-204 study, 304 patients with relapsed/refractory classic Hodgkin lymphoma were randomized to receive either pembrolizumab 200 mg or brentuximab at 1.8 mg/kg intravenously every 3 weeks for up to 35 cycles.

The median age of patients was 36 years in the pembrolizumab arm and 35 years in the brentuximab vedotin arm, according to the report. Approximately 37% of the patients had previously undergone autologous SCT. About 40% had been refractory to frontline therapy, while 28% relapsed within 12 months of therapy and 32% relapsed later than 12 months.

Median PFS by blinded independent central review was 13.2 versus 8.3 months in the pembrolizumab and brentuximab arms, respectively (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88; P = .00271), Dr. Kuruvilla reported.

The benefit extended to “key subgroups” in the trial, he added, including those who were ineligible for autologous SCT, those with primary refractory disease, and those who were naive to brentuximab vedotin, with HRs of 0.61, 0.52, and 0.67, respectively.

Pembrolizumab was also associated with more durable responses versus brentuximab vedotin, according to the investigator.

The overall response rate was 65.6% and 54.2%, respectively, for pembrolizumab and brentuximab, although this difference of approximately 11 percentage points did not meet criteria for statistical significance, he said. Duration of response was 20.7 months or pembrolizumab and 13.8 months for brentuximab.

The rate of serious treatment-related adverse events was similar between groups, according to Dr. Kuruvilla, who reported grade 3-5 events occurring in 19.6% and 25.0% of the pembrolizumab and brentuximab arms. Serious treatment-related adverse events were numerically more frequent in the pembrolizumab arm (16.2% vs. 10.5%) and there was one treatment-related death caused by pneumonia, seen in the pembrolizumab arm.

Pneumonitis occurred in 2.6% of the brentuximab-treated patients and in 10.8% of pembrolizumab-treated patients, of which half of cases were grade 3-4, according to the report.

In the pembrolizumab arm, pneumonitis was felt to be drug-related in 15 of 16 cases, according to Dr. Kuruvilla, who added that 15 of 16 patients required corticosteroid therapy. “This has led to the resolution of the pneumonitis in 12 of 16 patients, with ongoing resolution in one further patient.”

Research funding for KEYNOTE-204 came from Merck Sharp & Dohme. Dr. Kuruvilla provided disclosures related to Merck and a variety of other pharmaceutical companies. Dr. Roschewski said he had no relationships to disclose.

SOURCE: Kuruvilla J et al. ASCO 2020, Abstract 8005.

The combination of pyrotinib and capecitabine significantly prolonged progression-free survival (PFS), when compared with lapatinib and capecitabine, among patients with previously treated HER2-positive metastatic breast cancer in a phase 3 trial.

PFS was extended by nearly 6 months among patients who received pyrotinib, a novel pan-HER2 inhibitor, combined with capecitabine. Grade 3 diarrhea occurred in nearly 31% of patients receiving the pyrotinib-capecitabine combination, though none of the patients discontinued treatment due to this adverse event.

Binghe Xu, MD, PhD, of the National Cancer Center/Cancer Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, presented these results, from the phase 3 PHOEBE trial, as part of the American Society of Clinical Oncology virtual scientific program.
 

The value of pyrotinib

Although there are already many targeted therapies for HER2-positive metastatic breast cancer, accessibility can be an issue, with drugs such as pertuzumab and trastuzumab emtansine (T-DM1) not available in all regions of the world, according to Dr. Xu.

“Before we initiated this clinical trial, lapatinib plus capecitabine was the only second-line standard of care against HER2-positive metastatic breast cancer in China,” he said.

Based, in part, on results of the PHOEBE trial, the combination of pyrotinib and capecitabine was approved in China as a second-line standard of care for patients with HER2-positive metastatic breast cancer, according to Dr. Xu.

Pyrotinib has now demonstrated “clinical value” in two phase 3 clinical trials, but its value in relation to pertuzumab, T-DM1, tucatinib, trastuzumab deruxtecan, or neratinib is less clear, said Aleix Prat, MD, PhD, of Hospital Clinic of Barcelona.

“Also, in my opinion, the toxicity profile needs attention,” Dr. Prat said in a discussion of the PHOEBE results that was also part of the virtual ASCO meeting.

The 31% incidence of grade 3 diarrhea was “very similar,” he said, to what was seen in PHENIX, another phase 3 trial of pyrotinib plus capecitabine that was presented at the 2019 ASCO annual meeting (J Clin Oncol 37, 2019 suppl; abstr 1001).

“What is the current therapy landscape? In my opinion, today, the first line remains taxane, trastuzumab, and pertuzumab; the second line T-DM1; and the third line tucatinib, trastuzumab, and capecitabine, with other treatment strategies reserved for later lines,” Dr. Prat said.

Study details

PHOEBE included 267 patients with HER2-positive metastatic breast cancer. They had previously received trastuzumab and taxanes, and/or anthracyclines, with up to two prior lines of chemotherapy for metastatic disease.

The patients’ median age was 50 years, 79% had visceral metastases at screening, and about 26% had trastuzumab resistance, Dr. Xu said. Resistance was defined as relapse within 6 months after adjuvant treatment or progression within 3 months of treatment for metastatic disease.

A statistically significant and clinically meaningful improvement was seen in PFS, the primary endpoint of the study, Dr. Xu said.

Median PFS by blinded independent central review was 12.5 months for the pyrotinib-capecitabine combination, compared with 6.8 months for lapatinib-capecitabine (hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .0001).

The PFS benefit was consistently observed across all predefined subgroups, including by trastuzumab resistance.

In trastuzumab-resistant patients, the median PFS was 12.5 months for the pyrotinib combination and 6.9 months for the lapatinib combination (HR, 0.60; 95% CI, 0.29-1.21). In patients without trastuzumab resistance, the median PFS was 12.5 months and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21-0.51).

Although overall survival (OS) data were not yet mature, there was a “strong trend” toward a benefit with pyrotinib, Dr. Xu said. The 12-month OS rate was 91.3% for the pyrotinib combination and 77.4% for lapatinib. The median OS was not reached in either arm at the time of analysis.

Treatment-related adverse events of grade 3 or greater occurred in 57.5% of the pyrotinib arm and 34.1% of the lapatinib arm.

Diarrhea was the most common grade 3 or greater treatment-related adverse event, occurring in 30.6% of patients in the pyrotinib arm and 8.3% of those in the lapatinib arm. No grade 4 or 5 diarrhea was seen.

Overall, diarrhea occurred in 94.8% of patients in the pyrotinib arm and 62.1% of those in the lapatinib arm. However, pyrotinib-associated diarrhea was generally of low severity, occurred early, had a short duration, was reversible, and did not lead to treatment termination, according to Dr. Xu.

This study was funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Xu reported additional disclosures related to AstraZeneca, Eisai, Pfizer, and Roche. Dr. Prat disclosed relationships with Amgen, Daiichi Sankyo, Lilly, MSD Oncology, and other companies.

SOURCE: Xu B et al. ASCO 2020, Abstract 1003

The combination of pyrotinib and capecitabine significantly prolonged progression-free survival (PFS), when compared with lapatinib and capecitabine, among patients with previously treated HER2-positive metastatic breast cancer in a phase 3 trial.

PFS was extended by nearly 6 months among patients who received pyrotinib, a novel pan-HER2 inhibitor, combined with capecitabine. Grade 3 diarrhea occurred in nearly 31% of patients receiving the pyrotinib-capecitabine combination, though none of the patients discontinued treatment due to this adverse event.

Binghe Xu, MD, PhD, of the National Cancer Center/Cancer Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, presented these results, from the phase 3 PHOEBE trial, as part of the American Society of Clinical Oncology virtual scientific program.
 

The value of pyrotinib

Although there are already many targeted therapies for HER2-positive metastatic breast cancer, accessibility can be an issue, with drugs such as pertuzumab and trastuzumab emtansine (T-DM1) not available in all regions of the world, according to Dr. Xu.

“Before we initiated this clinical trial, lapatinib plus capecitabine was the only second-line standard of care against HER2-positive metastatic breast cancer in China,” he said.

Based, in part, on results of the PHOEBE trial, the combination of pyrotinib and capecitabine was approved in China as a second-line standard of care for patients with HER2-positive metastatic breast cancer, according to Dr. Xu.

Pyrotinib has now demonstrated “clinical value” in two phase 3 clinical trials, but its value in relation to pertuzumab, T-DM1, tucatinib, trastuzumab deruxtecan, or neratinib is less clear, said Aleix Prat, MD, PhD, of Hospital Clinic of Barcelona.

“Also, in my opinion, the toxicity profile needs attention,” Dr. Prat said in a discussion of the PHOEBE results that was also part of the virtual ASCO meeting.

The 31% incidence of grade 3 diarrhea was “very similar,” he said, to what was seen in PHENIX, another phase 3 trial of pyrotinib plus capecitabine that was presented at the 2019 ASCO annual meeting (J Clin Oncol 37, 2019 suppl; abstr 1001).

“What is the current therapy landscape? In my opinion, today, the first line remains taxane, trastuzumab, and pertuzumab; the second line T-DM1; and the third line tucatinib, trastuzumab, and capecitabine, with other treatment strategies reserved for later lines,” Dr. Prat said.

Study details

PHOEBE included 267 patients with HER2-positive metastatic breast cancer. They had previously received trastuzumab and taxanes, and/or anthracyclines, with up to two prior lines of chemotherapy for metastatic disease.

The patients’ median age was 50 years, 79% had visceral metastases at screening, and about 26% had trastuzumab resistance, Dr. Xu said. Resistance was defined as relapse within 6 months after adjuvant treatment or progression within 3 months of treatment for metastatic disease.

A statistically significant and clinically meaningful improvement was seen in PFS, the primary endpoint of the study, Dr. Xu said.

Median PFS by blinded independent central review was 12.5 months for the pyrotinib-capecitabine combination, compared with 6.8 months for lapatinib-capecitabine (hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .0001).

The PFS benefit was consistently observed across all predefined subgroups, including by trastuzumab resistance.

In trastuzumab-resistant patients, the median PFS was 12.5 months for the pyrotinib combination and 6.9 months for the lapatinib combination (HR, 0.60; 95% CI, 0.29-1.21). In patients without trastuzumab resistance, the median PFS was 12.5 months and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21-0.51).

Although overall survival (OS) data were not yet mature, there was a “strong trend” toward a benefit with pyrotinib, Dr. Xu said. The 12-month OS rate was 91.3% for the pyrotinib combination and 77.4% for lapatinib. The median OS was not reached in either arm at the time of analysis.

Treatment-related adverse events of grade 3 or greater occurred in 57.5% of the pyrotinib arm and 34.1% of the lapatinib arm.

Diarrhea was the most common grade 3 or greater treatment-related adverse event, occurring in 30.6% of patients in the pyrotinib arm and 8.3% of those in the lapatinib arm. No grade 4 or 5 diarrhea was seen.

Overall, diarrhea occurred in 94.8% of patients in the pyrotinib arm and 62.1% of those in the lapatinib arm. However, pyrotinib-associated diarrhea was generally of low severity, occurred early, had a short duration, was reversible, and did not lead to treatment termination, according to Dr. Xu.

This study was funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Xu reported additional disclosures related to AstraZeneca, Eisai, Pfizer, and Roche. Dr. Prat disclosed relationships with Amgen, Daiichi Sankyo, Lilly, MSD Oncology, and other companies.

SOURCE: Xu B et al. ASCO 2020, Abstract 1003

The combination of pyrotinib and capecitabine significantly prolonged progression-free survival (PFS), when compared with lapatinib and capecitabine, among patients with previously treated HER2-positive metastatic breast cancer in a phase 3 trial.

PFS was extended by nearly 6 months among patients who received pyrotinib, a novel pan-HER2 inhibitor, combined with capecitabine. Grade 3 diarrhea occurred in nearly 31% of patients receiving the pyrotinib-capecitabine combination, though none of the patients discontinued treatment due to this adverse event.

Binghe Xu, MD, PhD, of the National Cancer Center/Cancer Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, presented these results, from the phase 3 PHOEBE trial, as part of the American Society of Clinical Oncology virtual scientific program.
 

The value of pyrotinib

Although there are already many targeted therapies for HER2-positive metastatic breast cancer, accessibility can be an issue, with drugs such as pertuzumab and trastuzumab emtansine (T-DM1) not available in all regions of the world, according to Dr. Xu.

“Before we initiated this clinical trial, lapatinib plus capecitabine was the only second-line standard of care against HER2-positive metastatic breast cancer in China,” he said.

Based, in part, on results of the PHOEBE trial, the combination of pyrotinib and capecitabine was approved in China as a second-line standard of care for patients with HER2-positive metastatic breast cancer, according to Dr. Xu.

Pyrotinib has now demonstrated “clinical value” in two phase 3 clinical trials, but its value in relation to pertuzumab, T-DM1, tucatinib, trastuzumab deruxtecan, or neratinib is less clear, said Aleix Prat, MD, PhD, of Hospital Clinic of Barcelona.

“Also, in my opinion, the toxicity profile needs attention,” Dr. Prat said in a discussion of the PHOEBE results that was also part of the virtual ASCO meeting.

The 31% incidence of grade 3 diarrhea was “very similar,” he said, to what was seen in PHENIX, another phase 3 trial of pyrotinib plus capecitabine that was presented at the 2019 ASCO annual meeting (J Clin Oncol 37, 2019 suppl; abstr 1001).

“What is the current therapy landscape? In my opinion, today, the first line remains taxane, trastuzumab, and pertuzumab; the second line T-DM1; and the third line tucatinib, trastuzumab, and capecitabine, with other treatment strategies reserved for later lines,” Dr. Prat said.

Study details

PHOEBE included 267 patients with HER2-positive metastatic breast cancer. They had previously received trastuzumab and taxanes, and/or anthracyclines, with up to two prior lines of chemotherapy for metastatic disease.

The patients’ median age was 50 years, 79% had visceral metastases at screening, and about 26% had trastuzumab resistance, Dr. Xu said. Resistance was defined as relapse within 6 months after adjuvant treatment or progression within 3 months of treatment for metastatic disease.

A statistically significant and clinically meaningful improvement was seen in PFS, the primary endpoint of the study, Dr. Xu said.

Median PFS by blinded independent central review was 12.5 months for the pyrotinib-capecitabine combination, compared with 6.8 months for lapatinib-capecitabine (hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .0001).

The PFS benefit was consistently observed across all predefined subgroups, including by trastuzumab resistance.

In trastuzumab-resistant patients, the median PFS was 12.5 months for the pyrotinib combination and 6.9 months for the lapatinib combination (HR, 0.60; 95% CI, 0.29-1.21). In patients without trastuzumab resistance, the median PFS was 12.5 months and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21-0.51).

Although overall survival (OS) data were not yet mature, there was a “strong trend” toward a benefit with pyrotinib, Dr. Xu said. The 12-month OS rate was 91.3% for the pyrotinib combination and 77.4% for lapatinib. The median OS was not reached in either arm at the time of analysis.

Treatment-related adverse events of grade 3 or greater occurred in 57.5% of the pyrotinib arm and 34.1% of the lapatinib arm.

Diarrhea was the most common grade 3 or greater treatment-related adverse event, occurring in 30.6% of patients in the pyrotinib arm and 8.3% of those in the lapatinib arm. No grade 4 or 5 diarrhea was seen.

Overall, diarrhea occurred in 94.8% of patients in the pyrotinib arm and 62.1% of those in the lapatinib arm. However, pyrotinib-associated diarrhea was generally of low severity, occurred early, had a short duration, was reversible, and did not lead to treatment termination, according to Dr. Xu.

This study was funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Xu reported additional disclosures related to AstraZeneca, Eisai, Pfizer, and Roche. Dr. Prat disclosed relationships with Amgen, Daiichi Sankyo, Lilly, MSD Oncology, and other companies.

SOURCE: Xu B et al. ASCO 2020, Abstract 1003

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.

For patients with high-risk locally advanced rectal cancer, a short course of radiotherapy followed by consolidative chemotherapy and then surgery significantly reduced the rate of treatment failure, compared with standard chemoradiotherapy, results of a randomized trial show.

The experimental approach cut risk of disease-related treatment failure at 3 years by 25%, driven primarily by a reduction in distant metastases, according to investigator Geke A.P. Hospers, MD, PhD.

The rate of pathological complete response (pCR) nearly doubled, from about 14% for the conventional approach to about 28% for short-course (25 Gy in 5 fractions) radiotherapy then CAPOX or FOLFOX4 followed by total mesorectal excision (TME), reported Dr. Hospers, a medical oncologist and professor at University Medical Center Groningen in the Netherlands.

Three-year survival was high at about 89% in both groups, she said, with no unexpected toxicity and no differences in surgery, postoperative complications, or quality of life.

Based on these results, the short-course radiotherapy followed by chemotherapy and TME “can be considered as a new standard of care,” Dr. Hospers and coauthors concluded in their report on the RAPIDO trial, which was of part of the American Society of Clinical Oncology virtual scientific program.

In agreement was Christopher L. Hallemeier, MD, who said in a virtual ASCO discussion of the RAPIDO trial that short-course radiotherapy followed by consolidative chemotherapy “is a standard option” for many patients and is, in fact, now endorsed in National Comprehensive Cancer Network (NCCN) guidelines.

“I should point out that 5 fractions of radiotherapy is COVID-19 friendly in that it reduces the number of visits to the health care facility,” said Dr. Hallemeier, of Mayo Clinic in Rochester, Minn.

Several questions remain, however, including whether clinicians should be concerned about a trend toward a higher risk of locoregional failure seen in the RAPIDO results and why there was a lack of difference in OS.

“Could it be we’re merely delaying distant metastases versus preventing them by more consistent use of systemic therapy sooner? Longer-term follow-up will be needed to determine whether that’s the case,” he said.

In RAPIDO, a total of 920 adult patients with adenocarcinoma of the rectum and high-risk features apparent on MRI were randomized to a standard chemoradiation arm or the experimental approach.

In the standard treatment arm, patients received chemoradiotherapy (28 fractions x 1.8 Gy or 25 fractions x 2 Gy combined with capecitabine) followed by surgery about 8 weeks later, then optional adjuvant chemotherapy (CAPOX for 8 courses or FOLFOX for 12 courses) in the centers where that approach was standard.

The experimental treatment consisted of short-course radiotherapy (5 fractions x 5 Gy) followed by chemotherapy (CAPOX for 6 courses or FOLFOX for 9 courses), then surgery 2-4 weeks later.

Disease-related treatment failure, the primary endpoint of the study, was significantly lower in the experimental arm, according to Dr. Hospers. The 3-year rate of disease-related treatment failure was 23.7% for the experimental treatment and 30.4% for standard chemoradiotherapy (hazard ratio, 0.75; 95% confidence interval, 0.60-0.96; P = .019).

According to Dr. Hospers, the difference in rates of treatment failure was primarily caused by a significant decrease in distant metastases, at 20% and 26.8% in the experimental and standard treatment arms, respectively, at 3 years (P = .005).

The rate of pCR was 28.4% for the experimental arm, versus 14.3% for standard treatment (P < .001), Dr. Hospers reported.

Grade 3 or greater neurologic toxicity was more common in the experimental arm, occurring in 4.3% versus 0.2% in the standard treatment arm, which Dr. Hospers said was expected because of the administration of oxaplatin. Likewise, there was a higher percentage of grade 3 or greater thromboembolic events in the experimental group (8.5% vs. 4.1%) and more grade 3 or greater diarrhea (17.6% vs. 9.3%).

Subgroup analysis showed that the experimental approach was favored over conventional chemoradiotherapy whether or not patients in the conventional arm went on to receive the optional adjuvant chemotherapy, according to Dr. Hospers.

Results of RAPIDO have the potential to change the standard of care for locally advanced rectal cancer, according to Suneel Kamath, MD, a gastrointestinal oncologist with Cleveland Clinic in Cleveland, Ohio.

The pCR rate with short-course radiation followed by chemotherapy is “excellent,” compared with what’s typically seen with standard, long-course chemoradiation, Dr. Kamath said in an interview.

“This proves that we don’t necessarily need long-course radiation for larger tumors or larger number of lymph nodes to get good down-staging,” he said.

The lower rate of distant metastatic disease with the short-course radiation and preoperative chemotherapy arm was also notable, Dr. Kamath said.

The study was sponsored by the University Medical Center Groningen. Dr. Hospers reported institutional disclosures related to Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche, and Seerave Foundation. Dr. Hallemeier reported honoraria and travel expenses from Focus Medical Communications and Imedex. Dr. Kamath had no relevant disclosures.

SOURCE: Hospers GAP et al. ASCO 2020, Abstract 4006.

For patients with high-risk locally advanced rectal cancer, a short course of radiotherapy followed by consolidative chemotherapy and then surgery significantly reduced the rate of treatment failure, compared with standard chemoradiotherapy, results of a randomized trial show.

The experimental approach cut risk of disease-related treatment failure at 3 years by 25%, driven primarily by a reduction in distant metastases, according to investigator Geke A.P. Hospers, MD, PhD.

The rate of pathological complete response (pCR) nearly doubled, from about 14% for the conventional approach to about 28% for short-course (25 Gy in 5 fractions) radiotherapy then CAPOX or FOLFOX4 followed by total mesorectal excision (TME), reported Dr. Hospers, a medical oncologist and professor at University Medical Center Groningen in the Netherlands.

Three-year survival was high at about 89% in both groups, she said, with no unexpected toxicity and no differences in surgery, postoperative complications, or quality of life.

Based on these results, the short-course radiotherapy followed by chemotherapy and TME “can be considered as a new standard of care,” Dr. Hospers and coauthors concluded in their report on the RAPIDO trial, which was of part of the American Society of Clinical Oncology virtual scientific program.

In agreement was Christopher L. Hallemeier, MD, who said in a virtual ASCO discussion of the RAPIDO trial that short-course radiotherapy followed by consolidative chemotherapy “is a standard option” for many patients and is, in fact, now endorsed in National Comprehensive Cancer Network (NCCN) guidelines.

“I should point out that 5 fractions of radiotherapy is COVID-19 friendly in that it reduces the number of visits to the health care facility,” said Dr. Hallemeier, of Mayo Clinic in Rochester, Minn.

Several questions remain, however, including whether clinicians should be concerned about a trend toward a higher risk of locoregional failure seen in the RAPIDO results and why there was a lack of difference in OS.

“Could it be we’re merely delaying distant metastases versus preventing them by more consistent use of systemic therapy sooner? Longer-term follow-up will be needed to determine whether that’s the case,” he said.

In RAPIDO, a total of 920 adult patients with adenocarcinoma of the rectum and high-risk features apparent on MRI were randomized to a standard chemoradiation arm or the experimental approach.

In the standard treatment arm, patients received chemoradiotherapy (28 fractions x 1.8 Gy or 25 fractions x 2 Gy combined with capecitabine) followed by surgery about 8 weeks later, then optional adjuvant chemotherapy (CAPOX for 8 courses or FOLFOX for 12 courses) in the centers where that approach was standard.

The experimental treatment consisted of short-course radiotherapy (5 fractions x 5 Gy) followed by chemotherapy (CAPOX for 6 courses or FOLFOX for 9 courses), then surgery 2-4 weeks later.

Disease-related treatment failure, the primary endpoint of the study, was significantly lower in the experimental arm, according to Dr. Hospers. The 3-year rate of disease-related treatment failure was 23.7% for the experimental treatment and 30.4% for standard chemoradiotherapy (hazard ratio, 0.75; 95% confidence interval, 0.60-0.96; P = .019).

According to Dr. Hospers, the difference in rates of treatment failure was primarily caused by a significant decrease in distant metastases, at 20% and 26.8% in the experimental and standard treatment arms, respectively, at 3 years (P = .005).

The rate of pCR was 28.4% for the experimental arm, versus 14.3% for standard treatment (P < .001), Dr. Hospers reported.

Grade 3 or greater neurologic toxicity was more common in the experimental arm, occurring in 4.3% versus 0.2% in the standard treatment arm, which Dr. Hospers said was expected because of the administration of oxaplatin. Likewise, there was a higher percentage of grade 3 or greater thromboembolic events in the experimental group (8.5% vs. 4.1%) and more grade 3 or greater diarrhea (17.6% vs. 9.3%).

Subgroup analysis showed that the experimental approach was favored over conventional chemoradiotherapy whether or not patients in the conventional arm went on to receive the optional adjuvant chemotherapy, according to Dr. Hospers.

Results of RAPIDO have the potential to change the standard of care for locally advanced rectal cancer, according to Suneel Kamath, MD, a gastrointestinal oncologist with Cleveland Clinic in Cleveland, Ohio.

The pCR rate with short-course radiation followed by chemotherapy is “excellent,” compared with what’s typically seen with standard, long-course chemoradiation, Dr. Kamath said in an interview.

“This proves that we don’t necessarily need long-course radiation for larger tumors or larger number of lymph nodes to get good down-staging,” he said.

The lower rate of distant metastatic disease with the short-course radiation and preoperative chemotherapy arm was also notable, Dr. Kamath said.

The study was sponsored by the University Medical Center Groningen. Dr. Hospers reported institutional disclosures related to Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche, and Seerave Foundation. Dr. Hallemeier reported honoraria and travel expenses from Focus Medical Communications and Imedex. Dr. Kamath had no relevant disclosures.

SOURCE: Hospers GAP et al. ASCO 2020, Abstract 4006.

For patients with high-risk locally advanced rectal cancer, a short course of radiotherapy followed by consolidative chemotherapy and then surgery significantly reduced the rate of treatment failure, compared with standard chemoradiotherapy, results of a randomized trial show.

The experimental approach cut risk of disease-related treatment failure at 3 years by 25%, driven primarily by a reduction in distant metastases, according to investigator Geke A.P. Hospers, MD, PhD.

The rate of pathological complete response (pCR) nearly doubled, from about 14% for the conventional approach to about 28% for short-course (25 Gy in 5 fractions) radiotherapy then CAPOX or FOLFOX4 followed by total mesorectal excision (TME), reported Dr. Hospers, a medical oncologist and professor at University Medical Center Groningen in the Netherlands.

Three-year survival was high at about 89% in both groups, she said, with no unexpected toxicity and no differences in surgery, postoperative complications, or quality of life.

Based on these results, the short-course radiotherapy followed by chemotherapy and TME “can be considered as a new standard of care,” Dr. Hospers and coauthors concluded in their report on the RAPIDO trial, which was of part of the American Society of Clinical Oncology virtual scientific program.

In agreement was Christopher L. Hallemeier, MD, who said in a virtual ASCO discussion of the RAPIDO trial that short-course radiotherapy followed by consolidative chemotherapy “is a standard option” for many patients and is, in fact, now endorsed in National Comprehensive Cancer Network (NCCN) guidelines.

“I should point out that 5 fractions of radiotherapy is COVID-19 friendly in that it reduces the number of visits to the health care facility,” said Dr. Hallemeier, of Mayo Clinic in Rochester, Minn.

Several questions remain, however, including whether clinicians should be concerned about a trend toward a higher risk of locoregional failure seen in the RAPIDO results and why there was a lack of difference in OS.

“Could it be we’re merely delaying distant metastases versus preventing them by more consistent use of systemic therapy sooner? Longer-term follow-up will be needed to determine whether that’s the case,” he said.

In RAPIDO, a total of 920 adult patients with adenocarcinoma of the rectum and high-risk features apparent on MRI were randomized to a standard chemoradiation arm or the experimental approach.

In the standard treatment arm, patients received chemoradiotherapy (28 fractions x 1.8 Gy or 25 fractions x 2 Gy combined with capecitabine) followed by surgery about 8 weeks later, then optional adjuvant chemotherapy (CAPOX for 8 courses or FOLFOX for 12 courses) in the centers where that approach was standard.

The experimental treatment consisted of short-course radiotherapy (5 fractions x 5 Gy) followed by chemotherapy (CAPOX for 6 courses or FOLFOX for 9 courses), then surgery 2-4 weeks later.

Disease-related treatment failure, the primary endpoint of the study, was significantly lower in the experimental arm, according to Dr. Hospers. The 3-year rate of disease-related treatment failure was 23.7% for the experimental treatment and 30.4% for standard chemoradiotherapy (hazard ratio, 0.75; 95% confidence interval, 0.60-0.96; P = .019).

According to Dr. Hospers, the difference in rates of treatment failure was primarily caused by a significant decrease in distant metastases, at 20% and 26.8% in the experimental and standard treatment arms, respectively, at 3 years (P = .005).

The rate of pCR was 28.4% for the experimental arm, versus 14.3% for standard treatment (P < .001), Dr. Hospers reported.

Grade 3 or greater neurologic toxicity was more common in the experimental arm, occurring in 4.3% versus 0.2% in the standard treatment arm, which Dr. Hospers said was expected because of the administration of oxaplatin. Likewise, there was a higher percentage of grade 3 or greater thromboembolic events in the experimental group (8.5% vs. 4.1%) and more grade 3 or greater diarrhea (17.6% vs. 9.3%).

Subgroup analysis showed that the experimental approach was favored over conventional chemoradiotherapy whether or not patients in the conventional arm went on to receive the optional adjuvant chemotherapy, according to Dr. Hospers.

Results of RAPIDO have the potential to change the standard of care for locally advanced rectal cancer, according to Suneel Kamath, MD, a gastrointestinal oncologist with Cleveland Clinic in Cleveland, Ohio.

The pCR rate with short-course radiation followed by chemotherapy is “excellent,” compared with what’s typically seen with standard, long-course chemoradiation, Dr. Kamath said in an interview.

“This proves that we don’t necessarily need long-course radiation for larger tumors or larger number of lymph nodes to get good down-staging,” he said.

The lower rate of distant metastatic disease with the short-course radiation and preoperative chemotherapy arm was also notable, Dr. Kamath said.

The study was sponsored by the University Medical Center Groningen. Dr. Hospers reported institutional disclosures related to Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche, and Seerave Foundation. Dr. Hallemeier reported honoraria and travel expenses from Focus Medical Communications and Imedex. Dr. Kamath had no relevant disclosures.

SOURCE: Hospers GAP et al. ASCO 2020, Abstract 4006.

Anthracyclines add toxicity with no evidence of improved survival in patients with HER2-positive breast cancer receiving a neoadjuvant chemotherapy regimen plus dual HER2 blockade, results of a  phase 3 trial have suggested.

Event-free survival (EFS) estimates at 3 years were 93% for patients receiving anthracycline-containing chemotherapy plus trastuzumab/pertuzumab and 94% for those receiving an anthracycline-free regimen, according to long-term follow-up results of TRAIN-2, a randomized, phase 3 trial.

There was also “no evidence” that higher-risk patients would benefit from anthracyclines, said investigator Anna Van der Voort of the Netherlands Cancer Institute in Amsterdam.

“Today, anthracyclines are often used, especially in patients with higher risk of recurrence,” said Ms. Van der Voort in her presentation, which was part of the American Society of Clinical Oncology (ASCO) virtual scientific program.

“Importantly, anthracyclines increased the risk of febrile neutropenia, cardiac toxicity, and chemotherapy-associated leukemia, and therefore, a neoadjuvant anthracycline-free regimen with dual HER2 blockade should be considered in all stage II and III HER2-positive breast cancer patients,” she suggested.

With these new results, there are now “great safety data and very promising efficacy data” from two comparative studies favoring nonanthracycline regimens plus HER2 blockade over an anthracycline approach, even in patients with disease thought to be at high risk of recurrence, said Sara A. Hurvitz, MD, associate professor of medicine at the University of California Los Angeles Jonsson Comprehensive Cancer Center.

The other comparative study, BCIRG-006, demonstrated that docetaxel and carboplatin plus trastuzumab (TCH) had similar efficacy, fewer acute toxicities, and less cardiotoxicity and leukemia than did doxorubicin/cyclophosphamide followed by docetaxel (AC-T).

In a follow-up analysis focused on patients with four or more positive lymph nodes, disease-free survival was similar for the nonanthracycline and anthracycline regimens, Dr. Hurvitz noted.

“I would challenge us to think carefully about the standard use of anthracyclines when we have so many targeted therapies available for our patients with HER2-positive disease now,” Dr. Hurvitz said in her commentary on TRAIN-2 that was also part of the virtual ASCO proceedings.

The TRAIN-2 trial included 438 patients in the Netherlands with previously untreated stage II to III HER2-positive breast cancer. Patients randomized to the anthracycline-containing arm received 5-fluorouracil, epirubicin, and cyclophosphamide in three 3-week cycles followed by paclitaxel and carboplatin in six 3-week cycles.

Patients in the anthracycline-free arm received paclitaxel and carboplatin for nine 3-week cycles. Both groups also received trastuzumab and pertuzumab concurrent with chemotherapy.

The pathological complete response (pCR) rate was high with and without anthracyclines, Ms. Van der Voort said, referring to primary results of TRAIN-2 previously published in Lancet Oncology.

In that report, pCR was seen in 67% of patients in the anthracycline group, and 68% in the nonanthracycline group (P = .95), a finding that was consistent regardless of tumor size, nodal status, or hormone receptor status, said Ms. Van der Voort. She added that significantly more febrile neutropenia and hypokalemia were seen in the anthracycline group.

At virtual ASCO, Ms. Van der Voort presented results of the EFS analysis. At the time of analysis, there were 21 events among 219 patients in the nonanthracycline group (10%) and 23 events among 219 patients in the anthracycline group (11%). The corresponding 3-year EFS estimates were 93.5% and 92.7%, with a hazard ratio that favored the nonanthracycline group, though the difference between arms was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.50-1.63).

“The results were independent of hormone receptor status, age, tumor size, nodal status, and grade, so we found no evidence that high-risk patients require anthracyclines,” said Ms. Van der Voort. Of note, results divided by nodal status suggested similar or better outcomes in the absence of anthracyclines, even in the highest-risk group, she added.

Estimated 3-year overall survival rates were likewise similar between groups, at 98.2% and 97.7% in the nonanthracycline and anthracycline arms, respectively.

Declines in left ventricular ejection fraction were more frequent in the anthracycline group (36% vs. 22% for the nonanthracycline group; P = .0016), and about one-third of patients did not recover that decline. New malignancies were found in 5% of the anthracycline group and 2% of the nonanthracycline group.

The TRAIN-2 study was sponsored by the Netherlands Cancer Institute and Roche. Ms. Van der Voort said she had no relationships to disclose. Dr. Hurwitz reported institutional research funding from multiple pharmaceutical companies including Genentech/Roche.

SOURCE: Van der Voort A et al. ASCO 2020, Abstract 501.

Anthracyclines add toxicity with no evidence of improved survival in patients with HER2-positive breast cancer receiving a neoadjuvant chemotherapy regimen plus dual HER2 blockade, results of a  phase 3 trial have suggested.

Event-free survival (EFS) estimates at 3 years were 93% for patients receiving anthracycline-containing chemotherapy plus trastuzumab/pertuzumab and 94% for those receiving an anthracycline-free regimen, according to long-term follow-up results of TRAIN-2, a randomized, phase 3 trial.

There was also “no evidence” that higher-risk patients would benefit from anthracyclines, said investigator Anna Van der Voort of the Netherlands Cancer Institute in Amsterdam.

“Today, anthracyclines are often used, especially in patients with higher risk of recurrence,” said Ms. Van der Voort in her presentation, which was part of the American Society of Clinical Oncology (ASCO) virtual scientific program.

“Importantly, anthracyclines increased the risk of febrile neutropenia, cardiac toxicity, and chemotherapy-associated leukemia, and therefore, a neoadjuvant anthracycline-free regimen with dual HER2 blockade should be considered in all stage II and III HER2-positive breast cancer patients,” she suggested.

With these new results, there are now “great safety data and very promising efficacy data” from two comparative studies favoring nonanthracycline regimens plus HER2 blockade over an anthracycline approach, even in patients with disease thought to be at high risk of recurrence, said Sara A. Hurvitz, MD, associate professor of medicine at the University of California Los Angeles Jonsson Comprehensive Cancer Center.

The other comparative study, BCIRG-006, demonstrated that docetaxel and carboplatin plus trastuzumab (TCH) had similar efficacy, fewer acute toxicities, and less cardiotoxicity and leukemia than did doxorubicin/cyclophosphamide followed by docetaxel (AC-T).

In a follow-up analysis focused on patients with four or more positive lymph nodes, disease-free survival was similar for the nonanthracycline and anthracycline regimens, Dr. Hurvitz noted.

“I would challenge us to think carefully about the standard use of anthracyclines when we have so many targeted therapies available for our patients with HER2-positive disease now,” Dr. Hurvitz said in her commentary on TRAIN-2 that was also part of the virtual ASCO proceedings.

The TRAIN-2 trial included 438 patients in the Netherlands with previously untreated stage II to III HER2-positive breast cancer. Patients randomized to the anthracycline-containing arm received 5-fluorouracil, epirubicin, and cyclophosphamide in three 3-week cycles followed by paclitaxel and carboplatin in six 3-week cycles.

Patients in the anthracycline-free arm received paclitaxel and carboplatin for nine 3-week cycles. Both groups also received trastuzumab and pertuzumab concurrent with chemotherapy.

The pathological complete response (pCR) rate was high with and without anthracyclines, Ms. Van der Voort said, referring to primary results of TRAIN-2 previously published in Lancet Oncology.

In that report, pCR was seen in 67% of patients in the anthracycline group, and 68% in the nonanthracycline group (P = .95), a finding that was consistent regardless of tumor size, nodal status, or hormone receptor status, said Ms. Van der Voort. She added that significantly more febrile neutropenia and hypokalemia were seen in the anthracycline group.

At virtual ASCO, Ms. Van der Voort presented results of the EFS analysis. At the time of analysis, there were 21 events among 219 patients in the nonanthracycline group (10%) and 23 events among 219 patients in the anthracycline group (11%). The corresponding 3-year EFS estimates were 93.5% and 92.7%, with a hazard ratio that favored the nonanthracycline group, though the difference between arms was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.50-1.63).

“The results were independent of hormone receptor status, age, tumor size, nodal status, and grade, so we found no evidence that high-risk patients require anthracyclines,” said Ms. Van der Voort. Of note, results divided by nodal status suggested similar or better outcomes in the absence of anthracyclines, even in the highest-risk group, she added.

Estimated 3-year overall survival rates were likewise similar between groups, at 98.2% and 97.7% in the nonanthracycline and anthracycline arms, respectively.

Declines in left ventricular ejection fraction were more frequent in the anthracycline group (36% vs. 22% for the nonanthracycline group; P = .0016), and about one-third of patients did not recover that decline. New malignancies were found in 5% of the anthracycline group and 2% of the nonanthracycline group.

The TRAIN-2 study was sponsored by the Netherlands Cancer Institute and Roche. Ms. Van der Voort said she had no relationships to disclose. Dr. Hurwitz reported institutional research funding from multiple pharmaceutical companies including Genentech/Roche.

SOURCE: Van der Voort A et al. ASCO 2020, Abstract 501.

Anthracyclines add toxicity with no evidence of improved survival in patients with HER2-positive breast cancer receiving a neoadjuvant chemotherapy regimen plus dual HER2 blockade, results of a  phase 3 trial have suggested.

Event-free survival (EFS) estimates at 3 years were 93% for patients receiving anthracycline-containing chemotherapy plus trastuzumab/pertuzumab and 94% for those receiving an anthracycline-free regimen, according to long-term follow-up results of TRAIN-2, a randomized, phase 3 trial.

There was also “no evidence” that higher-risk patients would benefit from anthracyclines, said investigator Anna Van der Voort of the Netherlands Cancer Institute in Amsterdam.

“Today, anthracyclines are often used, especially in patients with higher risk of recurrence,” said Ms. Van der Voort in her presentation, which was part of the American Society of Clinical Oncology (ASCO) virtual scientific program.

“Importantly, anthracyclines increased the risk of febrile neutropenia, cardiac toxicity, and chemotherapy-associated leukemia, and therefore, a neoadjuvant anthracycline-free regimen with dual HER2 blockade should be considered in all stage II and III HER2-positive breast cancer patients,” she suggested.

With these new results, there are now “great safety data and very promising efficacy data” from two comparative studies favoring nonanthracycline regimens plus HER2 blockade over an anthracycline approach, even in patients with disease thought to be at high risk of recurrence, said Sara A. Hurvitz, MD, associate professor of medicine at the University of California Los Angeles Jonsson Comprehensive Cancer Center.

The other comparative study, BCIRG-006, demonstrated that docetaxel and carboplatin plus trastuzumab (TCH) had similar efficacy, fewer acute toxicities, and less cardiotoxicity and leukemia than did doxorubicin/cyclophosphamide followed by docetaxel (AC-T).

In a follow-up analysis focused on patients with four or more positive lymph nodes, disease-free survival was similar for the nonanthracycline and anthracycline regimens, Dr. Hurvitz noted.

“I would challenge us to think carefully about the standard use of anthracyclines when we have so many targeted therapies available for our patients with HER2-positive disease now,” Dr. Hurvitz said in her commentary on TRAIN-2 that was also part of the virtual ASCO proceedings.

The TRAIN-2 trial included 438 patients in the Netherlands with previously untreated stage II to III HER2-positive breast cancer. Patients randomized to the anthracycline-containing arm received 5-fluorouracil, epirubicin, and cyclophosphamide in three 3-week cycles followed by paclitaxel and carboplatin in six 3-week cycles.

Patients in the anthracycline-free arm received paclitaxel and carboplatin for nine 3-week cycles. Both groups also received trastuzumab and pertuzumab concurrent with chemotherapy.

The pathological complete response (pCR) rate was high with and without anthracyclines, Ms. Van der Voort said, referring to primary results of TRAIN-2 previously published in Lancet Oncology.

In that report, pCR was seen in 67% of patients in the anthracycline group, and 68% in the nonanthracycline group (P = .95), a finding that was consistent regardless of tumor size, nodal status, or hormone receptor status, said Ms. Van der Voort. She added that significantly more febrile neutropenia and hypokalemia were seen in the anthracycline group.

At virtual ASCO, Ms. Van der Voort presented results of the EFS analysis. At the time of analysis, there were 21 events among 219 patients in the nonanthracycline group (10%) and 23 events among 219 patients in the anthracycline group (11%). The corresponding 3-year EFS estimates were 93.5% and 92.7%, with a hazard ratio that favored the nonanthracycline group, though the difference between arms was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.50-1.63).

“The results were independent of hormone receptor status, age, tumor size, nodal status, and grade, so we found no evidence that high-risk patients require anthracyclines,” said Ms. Van der Voort. Of note, results divided by nodal status suggested similar or better outcomes in the absence of anthracyclines, even in the highest-risk group, she added.

Estimated 3-year overall survival rates were likewise similar between groups, at 98.2% and 97.7% in the nonanthracycline and anthracycline arms, respectively.

Declines in left ventricular ejection fraction were more frequent in the anthracycline group (36% vs. 22% for the nonanthracycline group; P = .0016), and about one-third of patients did not recover that decline. New malignancies were found in 5% of the anthracycline group and 2% of the nonanthracycline group.

The TRAIN-2 study was sponsored by the Netherlands Cancer Institute and Roche. Ms. Van der Voort said she had no relationships to disclose. Dr. Hurwitz reported institutional research funding from multiple pharmaceutical companies including Genentech/Roche.

SOURCE: Van der Voort A et al. ASCO 2020, Abstract 501.

While nivolumab plus doublet chemotherapy was effective in extensive-stage small-cell lung cancer (ES-SCLC) in a recent randomized trial, the results might not be sufficient to change current clinical practice, in which two first-line chemo-immunotherapies are already approved and recommended, sources said.

Nivolumab added to platinum/etoposide doublet chemotherapy was well tolerated and significantly improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone, according to results of ECOG-ACRIN EA5161, a randomized, phase 2 trial including 160 patients with ES-SCLC.

Risks of progression and death were reduced by 32% and 27%, respectively, when the immune checkpoint inhibitor was given along with chemotherapy, according to data presented by investigator Ticiana A. Leal, MD, of the University of Wisconsin Carbone Cancer Center in Madison.

“Our study, EA5161, confirms the efficacy of nivolumab in extensive-stage small cell lung cancer,” Dr. Leal said in a presentation she gave as part of the American Society of Clinical Oncology virtual scientific program.

Nivolumab did demonstrate a clear PFS advantage in EA5161, but “more surprisingly for a small trial” it also showed a clear OS advantage, said Taofeek K. Owonikoko, MD, PhD, in a commentary on the study.

“While the study as currently reported is insufficient to change practice, it does however provide very strong data to make the combination of nivolumab and platinum doublet acceptable as a platform for future clinical trials,” he said in the commentary, which was also included in the virtual ASCO proceedings.

Going forward, it would be difficult to justify another nondefinitive randomized phase 2 chemo-immunotherapy trial, especially if there are no “immediate plans” for a confirmatory phase 3 trial, added Dr. Owonikoko, who is director of thoracic oncology at Winship Cancer Institute of Emory University in Atlanta.

Nivolumab wasn’t the only immune checkpoint with new first-line data in ES-SCLC at ASCO. In the randomized, double-blind, phase 3 KEYNOTE-604 trial, pembrolizumab added to etoposide and platinum significantly prolonged PFS and showed a trend toward improved OS. However, the significance threshold for OS was missed, according to the report.

While these pembrolizumab data are also insufficient to change today’s practice standards, results for both the pembrolizumab- and nivolumab-containing regimens are nevertheless compelling to support their use as a platform for new treatment strategies, according to Dr. Owonikoko.

With these new ASCO data, there are now randomized data confirming a benefit of immune checkpoint inhibitor–based regimens in ES-SCLC, according to Lauren A. Byers, MD, from the department of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston.

Immune checkpoint inhibitors that are approved by the Food and Drug Administration for first-line treatment of ES-SCLC include atezolizumab (in combination with carboplatin and etoposide) and durvalumab (in combination with either carboplatin or cisplatin plus etoposide). In current National Comprehensive Cancer Network (NCCN) guidelines, both are described as “preferred” regimens for primary or adjuvant therapy.

“A lot of times in oncology we have trials with similar drugs, and you get somewhat different answers in terms of the outcome of the trials, so we’re kind of trying to tease them apart,” Dr. Byers said in an interview.

“I think in this situation, we’ve got four studies, and they essentially are extremely similar in terms of the result, which just gives us even more confidence that there is benefit, at least for a subset of patients.”

The EA5161 study was developed to evaluate the role of nivolumab in ES-SCLC, Dr. Leal said in her virtual ASCO presentation.

Of the 160 patients enrolled and randomized, 145 were eligible and treated, including 75 in the nivolumab plus chemotherapy arm and 70 in the chemotherapy arm. Participants were evenly split between performance status 0 and 1, and little more than half of patients were women, and a median of five treatment cycles were delivered in each arm.

Median PFS, the primary end point of the trial, was 5.5 months for nivolumab plus chemotherapy versus 4.7 months for chemotherapy alone for all eligible and treated patients (hazard ratio, 0.68; 95% confidence interval, 0.48-1.00; P = .047). In the intent-to-treat population, median PFS was 5.5 and 4.6 months in the respective arms (HR, 0.65; 95% CI, 0.46-0.91; P = .012).

Median overall survival was 11.3 months and 9.3 months for the nivolumab plus chemotherapy and chemotherapy-only arms, respectively, for all eligible and treated patients (HR, 0.73; 95% CI, 0.49-1.1), and in the intent-to-treat population, median OS was 11.3 and 8.5 months for the respective arms (HR, 0.67; 95% CI, 0.46-0.98; P = .038).

The overall response rate was 52% for nivolumab plus chemotherapy and 47% for chemotherapy alone, with a median duration of response of 5.6 and 3.3 months, respectively, Dr. Leal reported.

Treatment was generally well tolerated in both arms, according to the investigator, with no safety signals observed. Toxicities resulting in death occurred in nine patients in the nivolumab plus chemotherapy arm and seven in the chemotherapy-only arm. “Most of the events were related to progression of disease,” Dr. Leal said.

While nivolumab and pembrolizumab’s use in the first-line setting may be uncertain, it is currently approved for metastatic SCLC that has progressed following platinum-based chemotherapy and at least one more line of therapy, according to the drug’s package insert.

The EA5161 study was sponsored by the National Cancer Institute. Dr. Leal provided disclosures related to AbbVie, AstraZeneca, Bayer, BeyondSpring, Bristol-Myers Squibb, Genentech, InvisionFirst Lung, Merck, Mirati, Novocure, and Takeda.

Dr. Owonikoko provided disclosures related to Bristol-Myers Squibb, Novartis, Celgene, Lilly, Sandoz, AbbVie, Eisai, and Takeda, among others. Dr. Byers reported disclosures related to Bristol-Myers Squibb, AstraZeneca, AbbVie, GenMab, PharmaMar, and Sierra Oncology, Tolero, Alethia, Merck, Jazz Pharmaceuticals, and Pfizer.

SOURCE: Leal TA et al. ASCO 2020, Abstract 9000.

While nivolumab plus doublet chemotherapy was effective in extensive-stage small-cell lung cancer (ES-SCLC) in a recent randomized trial, the results might not be sufficient to change current clinical practice, in which two first-line chemo-immunotherapies are already approved and recommended, sources said.

Nivolumab added to platinum/etoposide doublet chemotherapy was well tolerated and significantly improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone, according to results of ECOG-ACRIN EA5161, a randomized, phase 2 trial including 160 patients with ES-SCLC.

Risks of progression and death were reduced by 32% and 27%, respectively, when the immune checkpoint inhibitor was given along with chemotherapy, according to data presented by investigator Ticiana A. Leal, MD, of the University of Wisconsin Carbone Cancer Center in Madison.

“Our study, EA5161, confirms the efficacy of nivolumab in extensive-stage small cell lung cancer,” Dr. Leal said in a presentation she gave as part of the American Society of Clinical Oncology virtual scientific program.

Nivolumab did demonstrate a clear PFS advantage in EA5161, but “more surprisingly for a small trial” it also showed a clear OS advantage, said Taofeek K. Owonikoko, MD, PhD, in a commentary on the study.

“While the study as currently reported is insufficient to change practice, it does however provide very strong data to make the combination of nivolumab and platinum doublet acceptable as a platform for future clinical trials,” he said in the commentary, which was also included in the virtual ASCO proceedings.

Going forward, it would be difficult to justify another nondefinitive randomized phase 2 chemo-immunotherapy trial, especially if there are no “immediate plans” for a confirmatory phase 3 trial, added Dr. Owonikoko, who is director of thoracic oncology at Winship Cancer Institute of Emory University in Atlanta.

Nivolumab wasn’t the only immune checkpoint with new first-line data in ES-SCLC at ASCO. In the randomized, double-blind, phase 3 KEYNOTE-604 trial, pembrolizumab added to etoposide and platinum significantly prolonged PFS and showed a trend toward improved OS. However, the significance threshold for OS was missed, according to the report.

While these pembrolizumab data are also insufficient to change today’s practice standards, results for both the pembrolizumab- and nivolumab-containing regimens are nevertheless compelling to support their use as a platform for new treatment strategies, according to Dr. Owonikoko.

With these new ASCO data, there are now randomized data confirming a benefit of immune checkpoint inhibitor–based regimens in ES-SCLC, according to Lauren A. Byers, MD, from the department of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston.

Immune checkpoint inhibitors that are approved by the Food and Drug Administration for first-line treatment of ES-SCLC include atezolizumab (in combination with carboplatin and etoposide) and durvalumab (in combination with either carboplatin or cisplatin plus etoposide). In current National Comprehensive Cancer Network (NCCN) guidelines, both are described as “preferred” regimens for primary or adjuvant therapy.

“A lot of times in oncology we have trials with similar drugs, and you get somewhat different answers in terms of the outcome of the trials, so we’re kind of trying to tease them apart,” Dr. Byers said in an interview.

“I think in this situation, we’ve got four studies, and they essentially are extremely similar in terms of the result, which just gives us even more confidence that there is benefit, at least for a subset of patients.”

The EA5161 study was developed to evaluate the role of nivolumab in ES-SCLC, Dr. Leal said in her virtual ASCO presentation.

Of the 160 patients enrolled and randomized, 145 were eligible and treated, including 75 in the nivolumab plus chemotherapy arm and 70 in the chemotherapy arm. Participants were evenly split between performance status 0 and 1, and little more than half of patients were women, and a median of five treatment cycles were delivered in each arm.

Median PFS, the primary end point of the trial, was 5.5 months for nivolumab plus chemotherapy versus 4.7 months for chemotherapy alone for all eligible and treated patients (hazard ratio, 0.68; 95% confidence interval, 0.48-1.00; P = .047). In the intent-to-treat population, median PFS was 5.5 and 4.6 months in the respective arms (HR, 0.65; 95% CI, 0.46-0.91; P = .012).

Median overall survival was 11.3 months and 9.3 months for the nivolumab plus chemotherapy and chemotherapy-only arms, respectively, for all eligible and treated patients (HR, 0.73; 95% CI, 0.49-1.1), and in the intent-to-treat population, median OS was 11.3 and 8.5 months for the respective arms (HR, 0.67; 95% CI, 0.46-0.98; P = .038).

The overall response rate was 52% for nivolumab plus chemotherapy and 47% for chemotherapy alone, with a median duration of response of 5.6 and 3.3 months, respectively, Dr. Leal reported.

Treatment was generally well tolerated in both arms, according to the investigator, with no safety signals observed. Toxicities resulting in death occurred in nine patients in the nivolumab plus chemotherapy arm and seven in the chemotherapy-only arm. “Most of the events were related to progression of disease,” Dr. Leal said.

While nivolumab and pembrolizumab’s use in the first-line setting may be uncertain, it is currently approved for metastatic SCLC that has progressed following platinum-based chemotherapy and at least one more line of therapy, according to the drug’s package insert.

The EA5161 study was sponsored by the National Cancer Institute. Dr. Leal provided disclosures related to AbbVie, AstraZeneca, Bayer, BeyondSpring, Bristol-Myers Squibb, Genentech, InvisionFirst Lung, Merck, Mirati, Novocure, and Takeda.

Dr. Owonikoko provided disclosures related to Bristol-Myers Squibb, Novartis, Celgene, Lilly, Sandoz, AbbVie, Eisai, and Takeda, among others. Dr. Byers reported disclosures related to Bristol-Myers Squibb, AstraZeneca, AbbVie, GenMab, PharmaMar, and Sierra Oncology, Tolero, Alethia, Merck, Jazz Pharmaceuticals, and Pfizer.

SOURCE: Leal TA et al. ASCO 2020, Abstract 9000.

While nivolumab plus doublet chemotherapy was effective in extensive-stage small-cell lung cancer (ES-SCLC) in a recent randomized trial, the results might not be sufficient to change current clinical practice, in which two first-line chemo-immunotherapies are already approved and recommended, sources said.

Nivolumab added to platinum/etoposide doublet chemotherapy was well tolerated and significantly improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone, according to results of ECOG-ACRIN EA5161, a randomized, phase 2 trial including 160 patients with ES-SCLC.

Risks of progression and death were reduced by 32% and 27%, respectively, when the immune checkpoint inhibitor was given along with chemotherapy, according to data presented by investigator Ticiana A. Leal, MD, of the University of Wisconsin Carbone Cancer Center in Madison.

“Our study, EA5161, confirms the efficacy of nivolumab in extensive-stage small cell lung cancer,” Dr. Leal said in a presentation she gave as part of the American Society of Clinical Oncology virtual scientific program.

Nivolumab did demonstrate a clear PFS advantage in EA5161, but “more surprisingly for a small trial” it also showed a clear OS advantage, said Taofeek K. Owonikoko, MD, PhD, in a commentary on the study.

“While the study as currently reported is insufficient to change practice, it does however provide very strong data to make the combination of nivolumab and platinum doublet acceptable as a platform for future clinical trials,” he said in the commentary, which was also included in the virtual ASCO proceedings.

Going forward, it would be difficult to justify another nondefinitive randomized phase 2 chemo-immunotherapy trial, especially if there are no “immediate plans” for a confirmatory phase 3 trial, added Dr. Owonikoko, who is director of thoracic oncology at Winship Cancer Institute of Emory University in Atlanta.

Nivolumab wasn’t the only immune checkpoint with new first-line data in ES-SCLC at ASCO. In the randomized, double-blind, phase 3 KEYNOTE-604 trial, pembrolizumab added to etoposide and platinum significantly prolonged PFS and showed a trend toward improved OS. However, the significance threshold for OS was missed, according to the report.

While these pembrolizumab data are also insufficient to change today’s practice standards, results for both the pembrolizumab- and nivolumab-containing regimens are nevertheless compelling to support their use as a platform for new treatment strategies, according to Dr. Owonikoko.

With these new ASCO data, there are now randomized data confirming a benefit of immune checkpoint inhibitor–based regimens in ES-SCLC, according to Lauren A. Byers, MD, from the department of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston.

Immune checkpoint inhibitors that are approved by the Food and Drug Administration for first-line treatment of ES-SCLC include atezolizumab (in combination with carboplatin and etoposide) and durvalumab (in combination with either carboplatin or cisplatin plus etoposide). In current National Comprehensive Cancer Network (NCCN) guidelines, both are described as “preferred” regimens for primary or adjuvant therapy.

“A lot of times in oncology we have trials with similar drugs, and you get somewhat different answers in terms of the outcome of the trials, so we’re kind of trying to tease them apart,” Dr. Byers said in an interview.

“I think in this situation, we’ve got four studies, and they essentially are extremely similar in terms of the result, which just gives us even more confidence that there is benefit, at least for a subset of patients.”

The EA5161 study was developed to evaluate the role of nivolumab in ES-SCLC, Dr. Leal said in her virtual ASCO presentation.

Of the 160 patients enrolled and randomized, 145 were eligible and treated, including 75 in the nivolumab plus chemotherapy arm and 70 in the chemotherapy arm. Participants were evenly split between performance status 0 and 1, and little more than half of patients were women, and a median of five treatment cycles were delivered in each arm.

Median PFS, the primary end point of the trial, was 5.5 months for nivolumab plus chemotherapy versus 4.7 months for chemotherapy alone for all eligible and treated patients (hazard ratio, 0.68; 95% confidence interval, 0.48-1.00; P = .047). In the intent-to-treat population, median PFS was 5.5 and 4.6 months in the respective arms (HR, 0.65; 95% CI, 0.46-0.91; P = .012).

Median overall survival was 11.3 months and 9.3 months for the nivolumab plus chemotherapy and chemotherapy-only arms, respectively, for all eligible and treated patients (HR, 0.73; 95% CI, 0.49-1.1), and in the intent-to-treat population, median OS was 11.3 and 8.5 months for the respective arms (HR, 0.67; 95% CI, 0.46-0.98; P = .038).

The overall response rate was 52% for nivolumab plus chemotherapy and 47% for chemotherapy alone, with a median duration of response of 5.6 and 3.3 months, respectively, Dr. Leal reported.

Treatment was generally well tolerated in both arms, according to the investigator, with no safety signals observed. Toxicities resulting in death occurred in nine patients in the nivolumab plus chemotherapy arm and seven in the chemotherapy-only arm. “Most of the events were related to progression of disease,” Dr. Leal said.

While nivolumab and pembrolizumab’s use in the first-line setting may be uncertain, it is currently approved for metastatic SCLC that has progressed following platinum-based chemotherapy and at least one more line of therapy, according to the drug’s package insert.

The EA5161 study was sponsored by the National Cancer Institute. Dr. Leal provided disclosures related to AbbVie, AstraZeneca, Bayer, BeyondSpring, Bristol-Myers Squibb, Genentech, InvisionFirst Lung, Merck, Mirati, Novocure, and Takeda.

Dr. Owonikoko provided disclosures related to Bristol-Myers Squibb, Novartis, Celgene, Lilly, Sandoz, AbbVie, Eisai, and Takeda, among others. Dr. Byers reported disclosures related to Bristol-Myers Squibb, AstraZeneca, AbbVie, GenMab, PharmaMar, and Sierra Oncology, Tolero, Alethia, Merck, Jazz Pharmaceuticals, and Pfizer.

SOURCE: Leal TA et al. ASCO 2020, Abstract 9000.

Among patients with atrial fibrillation, use of direct oral anticoagulants is linked to lower osteoporotic fracture risk versus warfarin, results of a recent population-based cohort study show.

iStock/Thinkstock

The choice of direct oral anticoagulant (DOAC) didn’t appear to have an impact, as each individual agent yielded a substantially lower risk of fracture versus the vitamin K antagonist, with risk reductions ranging from 38% to 48%, according to the study authors.

This is one of the latest reports to suggest DOACs could have an edge over warfarin for preventing fractures, providing new evidence that “may help inform the benefit risk assessment” when it comes to choosing an anticoagulant for a patient with atrial fibrillation (AFib) in the clinic, wrote the authors, led by Wallis C.Y. Lau, PhD, with the University College London.

“There exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” Dr. Lau and coauthors wrote in a report on the study that appears in Annals of Internal Medicine.

The case is especially compelling since fracture risk is “often neglected” when choosing an anticoagulant, the authors wrote. Surgeries to treat fracture are difficult because of the need for perioperative management of anticoagulation as “a balance between the risk for stroke and excessive bleeding must be achieved,” they added.

Based on these data, physicians should strongly consider DOACs as an alternative to vitamin K antagonists to reduce the risk of osteoporosis over the long term in patients with AFib, according to Victor Lawrence Roberts, MD, a Florida endocrinologist.

“Osteoporosis takes years, sometimes decades to develop, and if you then overlay warfarin on top of a readily evolving metabolic bone disease, you probably accelerate that process, said Dr. Roberts, professor of internal medicine at the University of Central Florida, Orlando, and editorial advisory board member of Internal Medicine News.

There’s a considerable amount of concerning preclinical data that warfarin could increase osteoporotic fracture risk. Of note, vitamin K antagonists modulate osteocalcin, a calcium-binding bone matrix protein, Dr. Roberts said.

“Osteocalcin is important for bone metabolism and health, and inhibiting osteocalcin will inhibit the ability to have a healthy bone matrix,” he explained.

The impact of anticoagulants on fracture risk is particularly relevant to patients with AFib, according to Dr. Lau and colleagues, who referenced one 2017 report showing a higher incidence of hip fracture among AFib patients versus those without AFib.

In their more recent study, Dr. Lau and colleagues reviewed electronic health records in a Hong Kong database for 23,515 older adults with a new diagnosis of AFib who received a new prescription of warfarin or DOACs including apixaban, dabigatran, or rivaroxaban.

DOAC use was consistently associated with a lower risk of osteoporotic fractures versus warfarin, regardless of the DOAC considered. The hazard ratios were 0.62 (95% confidence interval, 0.41-0.94) for apixaban, 0.65 (95% CI, 0.49-0.86) for dabigatran, and 0.52 (95% CI, 0.37-0.73) for rivaroxaban versus warfarin, the report showed.

Head-to-head comparisons between DOACS didn’t yield any statistically significant differences, though the analyses were underpowered in this respect, according to the investigators.

“This study can only rule out more than a twofold higher or a 50% lower relative risk for osteoporotic fractures between individual DOACs,” they wrote. “However, any absolute risk differences were small and would likely be of minor clinical significance.”

The reduced risk of fracture for DOACs versus warfarin was consistent in men and women with AFib, suggesting that women may particularly benefit from DOACs, given that they have a higher risk of fracture than men, the investigators added.

The results of this study suggest yet another benefit of DOACs over warfarin in patients with AFib, according to internist Noel Deep, MD, who is the chief medical officer of Aspirus Langlade Hospital in Antigo, Wisconsin.

“The lower risk of osteoporotic fractures with DOACS, in addition to other advantages such as lower risk of intracranial bleeding, once- or twice-daily consistent dosing, no dietary restrictions, and no blood tests to regulate the dose might be another reason that physicians may favor them over warfarin in older individuals requiring anticoagulation,” Dr. Deep said in an interview.

Results of this and several other recent studies may help in recommending DOACs to internal medicine patients who have a diagnosis of AFib requiring anticoagulation, according to Dr. Deep, who is also a physician at Aspirus Antigo Clinic and a member of Internal Medicine News’ editorial advisory board. These include a 2019 U.S.-based study of more than 167,000 patients with AFib (JAMA Intern Med. 2019;180[2]:245‐253) showing that use of DOACs, particularly apixaban, were linked to lower fracture risk versus warfarin use. Similarly, a Danish national registry study also published in 2019 showed that the absolute risk of osteoporotic fractures was low overall and significantly lower in patients who received DOACs (J Am Coll Cardiol. 2019;74[17]:2150-2158).

Funding for the study came from the University of Hong Kong and University College London Strategic Planning Fund. The study authors reported disclosures related to Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, IQVIA, and others.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 18. doi: 10.7326/M19-3671.

Among patients with atrial fibrillation, use of direct oral anticoagulants is linked to lower osteoporotic fracture risk versus warfarin, results of a recent population-based cohort study show.

iStock/Thinkstock

The choice of direct oral anticoagulant (DOAC) didn’t appear to have an impact, as each individual agent yielded a substantially lower risk of fracture versus the vitamin K antagonist, with risk reductions ranging from 38% to 48%, according to the study authors.

This is one of the latest reports to suggest DOACs could have an edge over warfarin for preventing fractures, providing new evidence that “may help inform the benefit risk assessment” when it comes to choosing an anticoagulant for a patient with atrial fibrillation (AFib) in the clinic, wrote the authors, led by Wallis C.Y. Lau, PhD, with the University College London.

“There exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” Dr. Lau and coauthors wrote in a report on the study that appears in Annals of Internal Medicine.

The case is especially compelling since fracture risk is “often neglected” when choosing an anticoagulant, the authors wrote. Surgeries to treat fracture are difficult because of the need for perioperative management of anticoagulation as “a balance between the risk for stroke and excessive bleeding must be achieved,” they added.

Based on these data, physicians should strongly consider DOACs as an alternative to vitamin K antagonists to reduce the risk of osteoporosis over the long term in patients with AFib, according to Victor Lawrence Roberts, MD, a Florida endocrinologist.

“Osteoporosis takes years, sometimes decades to develop, and if you then overlay warfarin on top of a readily evolving metabolic bone disease, you probably accelerate that process, said Dr. Roberts, professor of internal medicine at the University of Central Florida, Orlando, and editorial advisory board member of Internal Medicine News.

There’s a considerable amount of concerning preclinical data that warfarin could increase osteoporotic fracture risk. Of note, vitamin K antagonists modulate osteocalcin, a calcium-binding bone matrix protein, Dr. Roberts said.

“Osteocalcin is important for bone metabolism and health, and inhibiting osteocalcin will inhibit the ability to have a healthy bone matrix,” he explained.

The impact of anticoagulants on fracture risk is particularly relevant to patients with AFib, according to Dr. Lau and colleagues, who referenced one 2017 report showing a higher incidence of hip fracture among AFib patients versus those without AFib.

In their more recent study, Dr. Lau and colleagues reviewed electronic health records in a Hong Kong database for 23,515 older adults with a new diagnosis of AFib who received a new prescription of warfarin or DOACs including apixaban, dabigatran, or rivaroxaban.

DOAC use was consistently associated with a lower risk of osteoporotic fractures versus warfarin, regardless of the DOAC considered. The hazard ratios were 0.62 (95% confidence interval, 0.41-0.94) for apixaban, 0.65 (95% CI, 0.49-0.86) for dabigatran, and 0.52 (95% CI, 0.37-0.73) for rivaroxaban versus warfarin, the report showed.

Head-to-head comparisons between DOACS didn’t yield any statistically significant differences, though the analyses were underpowered in this respect, according to the investigators.

“This study can only rule out more than a twofold higher or a 50% lower relative risk for osteoporotic fractures between individual DOACs,” they wrote. “However, any absolute risk differences were small and would likely be of minor clinical significance.”

The reduced risk of fracture for DOACs versus warfarin was consistent in men and women with AFib, suggesting that women may particularly benefit from DOACs, given that they have a higher risk of fracture than men, the investigators added.

The results of this study suggest yet another benefit of DOACs over warfarin in patients with AFib, according to internist Noel Deep, MD, who is the chief medical officer of Aspirus Langlade Hospital in Antigo, Wisconsin.

“The lower risk of osteoporotic fractures with DOACS, in addition to other advantages such as lower risk of intracranial bleeding, once- or twice-daily consistent dosing, no dietary restrictions, and no blood tests to regulate the dose might be another reason that physicians may favor them over warfarin in older individuals requiring anticoagulation,” Dr. Deep said in an interview.

Results of this and several other recent studies may help in recommending DOACs to internal medicine patients who have a diagnosis of AFib requiring anticoagulation, according to Dr. Deep, who is also a physician at Aspirus Antigo Clinic and a member of Internal Medicine News’ editorial advisory board. These include a 2019 U.S.-based study of more than 167,000 patients with AFib (JAMA Intern Med. 2019;180[2]:245‐253) showing that use of DOACs, particularly apixaban, were linked to lower fracture risk versus warfarin use. Similarly, a Danish national registry study also published in 2019 showed that the absolute risk of osteoporotic fractures was low overall and significantly lower in patients who received DOACs (J Am Coll Cardiol. 2019;74[17]:2150-2158).

Funding for the study came from the University of Hong Kong and University College London Strategic Planning Fund. The study authors reported disclosures related to Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, IQVIA, and others.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 18. doi: 10.7326/M19-3671.

Among patients with atrial fibrillation, use of direct oral anticoagulants is linked to lower osteoporotic fracture risk versus warfarin, results of a recent population-based cohort study show.

iStock/Thinkstock

The choice of direct oral anticoagulant (DOAC) didn’t appear to have an impact, as each individual agent yielded a substantially lower risk of fracture versus the vitamin K antagonist, with risk reductions ranging from 38% to 48%, according to the study authors.

This is one of the latest reports to suggest DOACs could have an edge over warfarin for preventing fractures, providing new evidence that “may help inform the benefit risk assessment” when it comes to choosing an anticoagulant for a patient with atrial fibrillation (AFib) in the clinic, wrote the authors, led by Wallis C.Y. Lau, PhD, with the University College London.

“There exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” Dr. Lau and coauthors wrote in a report on the study that appears in Annals of Internal Medicine.

The case is especially compelling since fracture risk is “often neglected” when choosing an anticoagulant, the authors wrote. Surgeries to treat fracture are difficult because of the need for perioperative management of anticoagulation as “a balance between the risk for stroke and excessive bleeding must be achieved,” they added.

Based on these data, physicians should strongly consider DOACs as an alternative to vitamin K antagonists to reduce the risk of osteoporosis over the long term in patients with AFib, according to Victor Lawrence Roberts, MD, a Florida endocrinologist.

“Osteoporosis takes years, sometimes decades to develop, and if you then overlay warfarin on top of a readily evolving metabolic bone disease, you probably accelerate that process, said Dr. Roberts, professor of internal medicine at the University of Central Florida, Orlando, and editorial advisory board member of Internal Medicine News.

There’s a considerable amount of concerning preclinical data that warfarin could increase osteoporotic fracture risk. Of note, vitamin K antagonists modulate osteocalcin, a calcium-binding bone matrix protein, Dr. Roberts said.

“Osteocalcin is important for bone metabolism and health, and inhibiting osteocalcin will inhibit the ability to have a healthy bone matrix,” he explained.

The impact of anticoagulants on fracture risk is particularly relevant to patients with AFib, according to Dr. Lau and colleagues, who referenced one 2017 report showing a higher incidence of hip fracture among AFib patients versus those without AFib.

In their more recent study, Dr. Lau and colleagues reviewed electronic health records in a Hong Kong database for 23,515 older adults with a new diagnosis of AFib who received a new prescription of warfarin or DOACs including apixaban, dabigatran, or rivaroxaban.

DOAC use was consistently associated with a lower risk of osteoporotic fractures versus warfarin, regardless of the DOAC considered. The hazard ratios were 0.62 (95% confidence interval, 0.41-0.94) for apixaban, 0.65 (95% CI, 0.49-0.86) for dabigatran, and 0.52 (95% CI, 0.37-0.73) for rivaroxaban versus warfarin, the report showed.

Head-to-head comparisons between DOACS didn’t yield any statistically significant differences, though the analyses were underpowered in this respect, according to the investigators.

“This study can only rule out more than a twofold higher or a 50% lower relative risk for osteoporotic fractures between individual DOACs,” they wrote. “However, any absolute risk differences were small and would likely be of minor clinical significance.”

The reduced risk of fracture for DOACs versus warfarin was consistent in men and women with AFib, suggesting that women may particularly benefit from DOACs, given that they have a higher risk of fracture than men, the investigators added.

The results of this study suggest yet another benefit of DOACs over warfarin in patients with AFib, according to internist Noel Deep, MD, who is the chief medical officer of Aspirus Langlade Hospital in Antigo, Wisconsin.

“The lower risk of osteoporotic fractures with DOACS, in addition to other advantages such as lower risk of intracranial bleeding, once- or twice-daily consistent dosing, no dietary restrictions, and no blood tests to regulate the dose might be another reason that physicians may favor them over warfarin in older individuals requiring anticoagulation,” Dr. Deep said in an interview.

Results of this and several other recent studies may help in recommending DOACs to internal medicine patients who have a diagnosis of AFib requiring anticoagulation, according to Dr. Deep, who is also a physician at Aspirus Antigo Clinic and a member of Internal Medicine News’ editorial advisory board. These include a 2019 U.S.-based study of more than 167,000 patients with AFib (JAMA Intern Med. 2019;180[2]:245‐253) showing that use of DOACs, particularly apixaban, were linked to lower fracture risk versus warfarin use. Similarly, a Danish national registry study also published in 2019 showed that the absolute risk of osteoporotic fractures was low overall and significantly lower in patients who received DOACs (J Am Coll Cardiol. 2019;74[17]:2150-2158).

Funding for the study came from the University of Hong Kong and University College London Strategic Planning Fund. The study authors reported disclosures related to Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, IQVIA, and others.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 18. doi: 10.7326/M19-3671.