Conference Coverage

A HER3-targeted therapy has demonstrated clinically meaningful and durable efficacy in heavily pretreated patients with EGFR-mutant non–small cell lung cancer, according to results of a phase 1 study.

Patritumab deruxtecan, an antibody-drug conjugate targeting HER3, had an overall response rate (ORR) of 39% and median progression-free survival (PFS) of 8.2 months in a phase 1 study that included patients previously treated with tyrosine kinase inhibitors (TKIs) and chemotherapy, the results show.

The efficacy was seen across EGFR TKI resistance mechanisms in this very difficult-to-treat patient population, according to investigator Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute, Boston.

“There is not one category of individuals that are having a response, or not having a response,” Dr. Jänne said in a presentation at the annual meeting of the American Society of Clinical Oncology (Abstract 9007).

“Responses are observed in patients with identifiable resistance mechanisms, and in patients that do not have an identifiable resistance mechanism, but have progressed on prior EGFR TKI therapy,” he added.

More than 80% of non–small cell lung cancer (NSCLC) tumors express HER3, and of note, HER3 alterations do not appear to confer resistance to EGFR TKIs in patients with EGFR-mutant NSCLC, according to Dr. Jänne.
 

Study details

Also known as HER3-DXd, patritumab deruxtecan consists of a fully human anti-HER3 monoclonal antibody linked to a topoisomerase inhibitor payload by a tetrapeptide-based cleavable linker.

The antibody-drug conjugate is also being evaluated in metastatic breast cancer and colorectal cancer, Dr. Jänne said.

In the present phase 1 dose escalation and dose expansion study, a total of 57 patients were treated with patritumab deruxtecan at 5.6 mg/kg, the recommended dose for the expansion phase.

The median age of these patients was 65 years, and the majority (63%) were women, Dr. Jänne reported. About half had a history of central nervous system metastases.

The median number of prior lines of systemic therapy was four, making this a heavily pretreated patient population, Dr. Jänne said. All patients had received prior EGFR TKI therapy, and 86% specifically had prior osimertinib. Ninety-one percent had prior platinum-based chemotherapy, and 40% had received immunotherapy.
 

Spectrum of responses

The confirmed ORR of 39% included 1 complete response (2%) and 21 partial responses (37%), Dr. Jänne reported. The disease control rate was 72%, and median duration of response was 6.9 months at a median follow-up of 10.2 months.

The median PFS was 8.2 months in 57 patients overall and in a subset of 44 patients who had received prior osimertinib and platinum-based chemotherapy, according to the report.

Activity of patritumab deruxtecan was seen not only across patients with diverse mechanisms of EGFR TKI resistance, but also regardless of prior number of treatments, and regardless of history of brain metastases, the investigator said.

In addition, clinical responses were seen across a spectrum of baseline HER3 expression by immunohistochemistry, the investigator added.

Safety was assessed in 81 patients treated at a range of doses in the phase 1 trial. The most common grade 3 or greater treatment-emergent adverse events, observed in 5% or more of patients, included thrombocytopenia, neutropenia, and anemia, while other side effects such as fatigue and dyspnea were observed, Dr. Jänne said. About 9% of the adverse events led to treatment discontinuation in the safety cohort.

Interstitial lung disease was observed in four patients, or 5% of the safety cohort. Three of these were grade 1-2 and one was grade 3, according to the report.
 

Questions to explore

The efficacy of patritumab deruxtecan was “high” in this phase 1 study, based on the reported response rate and median PFS, said discussant Nicolas Girard, MD, PhD, of Institut Curie in Paris.

However, the most striking finding of the study was the efficacy of the antibody-drug conjugate across all reported resistance mechanisms, Dr. Girard said in his remarks.

Questions that remains to be explored, according to Dr. Girard, include the impact of previous treatment sequencing with TKIs and chemotherapy on patient outcomes with patritumab deruxtecan, as well as the assessment of intracranial response and PFS for patients treated with the agent.

In addition, antitumor activity was seen across a wide range of baseline HER3 expression levels in this study, suggesting that a predictive biomarker remains to be identified, according to Dr. Girard.

“HER3 immunohistochemistry does not seem to be the candidate in this setting,” he said.

The study was sponsored by Daiichi Sankyo. Dr. Jänne reported disclosures related to Daiichi Sankyo, as well as Araxes Pharma, Astellas Pharma, AstraZeneca, and multiple other pharmaceutical companies. Dr. Jänne is also coinventor on a Dana Farber Cancer Institute–owned patent on EGFR mutations licensed to Labcorp and receives postmarketing royalties from this invention.

Dr. Girard reported disclosures related to AbbVie, AstraZeneca, Boehringer Ingelheim, and multiple other pharmaceutical companies.

A HER3-targeted therapy has demonstrated clinically meaningful and durable efficacy in heavily pretreated patients with EGFR-mutant non–small cell lung cancer, according to results of a phase 1 study.

Patritumab deruxtecan, an antibody-drug conjugate targeting HER3, had an overall response rate (ORR) of 39% and median progression-free survival (PFS) of 8.2 months in a phase 1 study that included patients previously treated with tyrosine kinase inhibitors (TKIs) and chemotherapy, the results show.

The efficacy was seen across EGFR TKI resistance mechanisms in this very difficult-to-treat patient population, according to investigator Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute, Boston.

“There is not one category of individuals that are having a response, or not having a response,” Dr. Jänne said in a presentation at the annual meeting of the American Society of Clinical Oncology (Abstract 9007).

“Responses are observed in patients with identifiable resistance mechanisms, and in patients that do not have an identifiable resistance mechanism, but have progressed on prior EGFR TKI therapy,” he added.

More than 80% of non–small cell lung cancer (NSCLC) tumors express HER3, and of note, HER3 alterations do not appear to confer resistance to EGFR TKIs in patients with EGFR-mutant NSCLC, according to Dr. Jänne.
 

Study details

Also known as HER3-DXd, patritumab deruxtecan consists of a fully human anti-HER3 monoclonal antibody linked to a topoisomerase inhibitor payload by a tetrapeptide-based cleavable linker.

The antibody-drug conjugate is also being evaluated in metastatic breast cancer and colorectal cancer, Dr. Jänne said.

In the present phase 1 dose escalation and dose expansion study, a total of 57 patients were treated with patritumab deruxtecan at 5.6 mg/kg, the recommended dose for the expansion phase.

The median age of these patients was 65 years, and the majority (63%) were women, Dr. Jänne reported. About half had a history of central nervous system metastases.

The median number of prior lines of systemic therapy was four, making this a heavily pretreated patient population, Dr. Jänne said. All patients had received prior EGFR TKI therapy, and 86% specifically had prior osimertinib. Ninety-one percent had prior platinum-based chemotherapy, and 40% had received immunotherapy.
 

Spectrum of responses

The confirmed ORR of 39% included 1 complete response (2%) and 21 partial responses (37%), Dr. Jänne reported. The disease control rate was 72%, and median duration of response was 6.9 months at a median follow-up of 10.2 months.

The median PFS was 8.2 months in 57 patients overall and in a subset of 44 patients who had received prior osimertinib and platinum-based chemotherapy, according to the report.

Activity of patritumab deruxtecan was seen not only across patients with diverse mechanisms of EGFR TKI resistance, but also regardless of prior number of treatments, and regardless of history of brain metastases, the investigator said.

In addition, clinical responses were seen across a spectrum of baseline HER3 expression by immunohistochemistry, the investigator added.

Safety was assessed in 81 patients treated at a range of doses in the phase 1 trial. The most common grade 3 or greater treatment-emergent adverse events, observed in 5% or more of patients, included thrombocytopenia, neutropenia, and anemia, while other side effects such as fatigue and dyspnea were observed, Dr. Jänne said. About 9% of the adverse events led to treatment discontinuation in the safety cohort.

Interstitial lung disease was observed in four patients, or 5% of the safety cohort. Three of these were grade 1-2 and one was grade 3, according to the report.
 

Questions to explore

The efficacy of patritumab deruxtecan was “high” in this phase 1 study, based on the reported response rate and median PFS, said discussant Nicolas Girard, MD, PhD, of Institut Curie in Paris.

However, the most striking finding of the study was the efficacy of the antibody-drug conjugate across all reported resistance mechanisms, Dr. Girard said in his remarks.

Questions that remains to be explored, according to Dr. Girard, include the impact of previous treatment sequencing with TKIs and chemotherapy on patient outcomes with patritumab deruxtecan, as well as the assessment of intracranial response and PFS for patients treated with the agent.

In addition, antitumor activity was seen across a wide range of baseline HER3 expression levels in this study, suggesting that a predictive biomarker remains to be identified, according to Dr. Girard.

“HER3 immunohistochemistry does not seem to be the candidate in this setting,” he said.

The study was sponsored by Daiichi Sankyo. Dr. Jänne reported disclosures related to Daiichi Sankyo, as well as Araxes Pharma, Astellas Pharma, AstraZeneca, and multiple other pharmaceutical companies. Dr. Jänne is also coinventor on a Dana Farber Cancer Institute–owned patent on EGFR mutations licensed to Labcorp and receives postmarketing royalties from this invention.

Dr. Girard reported disclosures related to AbbVie, AstraZeneca, Boehringer Ingelheim, and multiple other pharmaceutical companies.

A HER3-targeted therapy has demonstrated clinically meaningful and durable efficacy in heavily pretreated patients with EGFR-mutant non–small cell lung cancer, according to results of a phase 1 study.

Patritumab deruxtecan, an antibody-drug conjugate targeting HER3, had an overall response rate (ORR) of 39% and median progression-free survival (PFS) of 8.2 months in a phase 1 study that included patients previously treated with tyrosine kinase inhibitors (TKIs) and chemotherapy, the results show.

The efficacy was seen across EGFR TKI resistance mechanisms in this very difficult-to-treat patient population, according to investigator Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute, Boston.

“There is not one category of individuals that are having a response, or not having a response,” Dr. Jänne said in a presentation at the annual meeting of the American Society of Clinical Oncology (Abstract 9007).

“Responses are observed in patients with identifiable resistance mechanisms, and in patients that do not have an identifiable resistance mechanism, but have progressed on prior EGFR TKI therapy,” he added.

More than 80% of non–small cell lung cancer (NSCLC) tumors express HER3, and of note, HER3 alterations do not appear to confer resistance to EGFR TKIs in patients with EGFR-mutant NSCLC, according to Dr. Jänne.
 

Study details

Also known as HER3-DXd, patritumab deruxtecan consists of a fully human anti-HER3 monoclonal antibody linked to a topoisomerase inhibitor payload by a tetrapeptide-based cleavable linker.

The antibody-drug conjugate is also being evaluated in metastatic breast cancer and colorectal cancer, Dr. Jänne said.

In the present phase 1 dose escalation and dose expansion study, a total of 57 patients were treated with patritumab deruxtecan at 5.6 mg/kg, the recommended dose for the expansion phase.

The median age of these patients was 65 years, and the majority (63%) were women, Dr. Jänne reported. About half had a history of central nervous system metastases.

The median number of prior lines of systemic therapy was four, making this a heavily pretreated patient population, Dr. Jänne said. All patients had received prior EGFR TKI therapy, and 86% specifically had prior osimertinib. Ninety-one percent had prior platinum-based chemotherapy, and 40% had received immunotherapy.
 

Spectrum of responses

The confirmed ORR of 39% included 1 complete response (2%) and 21 partial responses (37%), Dr. Jänne reported. The disease control rate was 72%, and median duration of response was 6.9 months at a median follow-up of 10.2 months.

The median PFS was 8.2 months in 57 patients overall and in a subset of 44 patients who had received prior osimertinib and platinum-based chemotherapy, according to the report.

Activity of patritumab deruxtecan was seen not only across patients with diverse mechanisms of EGFR TKI resistance, but also regardless of prior number of treatments, and regardless of history of brain metastases, the investigator said.

In addition, clinical responses were seen across a spectrum of baseline HER3 expression by immunohistochemistry, the investigator added.

Safety was assessed in 81 patients treated at a range of doses in the phase 1 trial. The most common grade 3 or greater treatment-emergent adverse events, observed in 5% or more of patients, included thrombocytopenia, neutropenia, and anemia, while other side effects such as fatigue and dyspnea were observed, Dr. Jänne said. About 9% of the adverse events led to treatment discontinuation in the safety cohort.

Interstitial lung disease was observed in four patients, or 5% of the safety cohort. Three of these were grade 1-2 and one was grade 3, according to the report.
 

Questions to explore

The efficacy of patritumab deruxtecan was “high” in this phase 1 study, based on the reported response rate and median PFS, said discussant Nicolas Girard, MD, PhD, of Institut Curie in Paris.

However, the most striking finding of the study was the efficacy of the antibody-drug conjugate across all reported resistance mechanisms, Dr. Girard said in his remarks.

Questions that remains to be explored, according to Dr. Girard, include the impact of previous treatment sequencing with TKIs and chemotherapy on patient outcomes with patritumab deruxtecan, as well as the assessment of intracranial response and PFS for patients treated with the agent.

In addition, antitumor activity was seen across a wide range of baseline HER3 expression levels in this study, suggesting that a predictive biomarker remains to be identified, according to Dr. Girard.

“HER3 immunohistochemistry does not seem to be the candidate in this setting,” he said.

The study was sponsored by Daiichi Sankyo. Dr. Jänne reported disclosures related to Daiichi Sankyo, as well as Araxes Pharma, Astellas Pharma, AstraZeneca, and multiple other pharmaceutical companies. Dr. Jänne is also coinventor on a Dana Farber Cancer Institute–owned patent on EGFR mutations licensed to Labcorp and receives postmarketing royalties from this invention.

Dr. Girard reported disclosures related to AbbVie, AstraZeneca, Boehringer Ingelheim, and multiple other pharmaceutical companies.

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

The relationship between adherence and benefit for those prescribed continuous positive airway pressure (CPAP) devices is clear. However, a Medicare-reimbursement rule that demands adherence blind to circumstances appears to be denying access to many low-income patients, according to an analysis delivered at the annual health policy and advocacy conference sponsored by the American College of Chest Physicians.

Over the past several years, adherence to CPAP has improved substantially following a series of studies that demonstrated the device must be used at least 4 hours per night to achieve improved outcomes. Medicare defines adherence as using the device more than 4 hours per night for 70% of nights (21 nights) during a consecutive 30-day period any time in the first 3 months of initial usage.

However, the studies that show improved adherence show a lag among those in the lowest income quartile, according to Sairam Parthasarathy, MD, director of the Center for Sleep and Circadian Sciences at the University of Arizona, Tucson.

When patients are followed for a year after being prescribed CPAP, the lag for the low-income patients is not seen immediately. Rather, adherence studies show a steady climb in adherence in all income groups initially, but ”right at 90 days there is a marked change,” said Dr. Parthasarathy.

This change happens to coincide with Medicare policy that denies reimbursement for CPAP after 90 days if patients are not using CPAP at least 4 hours per night, which is the threshold associated with benefit.

The correlation between this policy and income disparity is “observational” rather than proven, but Dr. Parthasarathy is confident it is valid. He believes it is a prime example of a health inequity driven by poorly conceived policy.

“The 90-day rule needs to go,” he said, calling the choice of threshold “man-made.” He added: “This is the only disease condition for which a therapy is withheld if it is not used according to some magical threshold. I cannot think of a more draconian policy.”

In an effort to illustrate the problem, he likened this policy to withholding insulin in a diabetes patient judged nonadherent because of a persistently elevated Hb1Ac.

At 90 days, adherence rates remain at a relatively early point in their upwards trajectory in all income groups. One year later, adherence rates are more than twice as high in the highest income relative to the lowest quartile and approaching twofold greater in quartiles 2 and 3.

“It takes time to get used to these devices,” Dr. Parthasarathy explained. Given studies demonstrating that “more is better” with CPAP, whether measured by sleep scales or quality of life, Dr. Parthasarathy advocates strategies to improve adherence, but he questioned an approach that penalizes low-income patients for a definition of nonadherence at an arbitrary point in time. He suggested it is just one example of health policies that ultimately penalize individuals with lower incomes.

“There are millions of dollars spent every year on understanding the genetics of disease, but the biggest influence on how long you live is the ZIP code of where you live,” said Dr. Parthasarathy, referring to ZIP codes as a surrogate for socioeconomic status.

This is not to imply, however, that genetics are irrelevant, Dr. Parthasarathy said. He pointed to data linking genetic traits that determine melanin levels and circadian rhythms. He noted one genotype associated with later bedtimes that is more commonly found in African-Americans and Hispanics. This has relevance to a variety of sleep disorders and other health conditions, but it might serve as a fundamental disadvantage for children with this genotype, Dr. Parthasarathy maintained. He cited a study conducted at his center that found Hispanic children sleep on average 30 minutes less than White children (Sleep Med 2016;18:61-6). The reason was simple. Hispanic children went to bed 30 minutes later but rose at the same time.

The later bedtimes and reduced sleep could potentially be one obstacle among many, such as the need for lower-income patients to hold several jobs, that prevent these patients from becoming accustomed to CPAP at the same speed as wealthier patients, according to Dr. Parthasarathy.

The current Medicare policy that withholds CPAP on the basis of a single definition of nonadherence appears to lead directly to an inequity in treatment of sleep apnea, he maintained. Dr. Parthasarathy, who was a coauthor of a recently published paper on addressing disparities in sleep health (Chest 2021;159:1232-40), described this issue as part of a larger problem of the failure to deliver health care that is sensitive to the cultural and racial differences underlying these inequities.

Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System, agreed. “This type of issue is exactly what our committee would like to address,” said Dr. Sarmiento, a member of the CHEST Health Policy and Advocacy Committee and the moderator of the session in which Dr. Parthasarathy presented his data.

Courtesy Dr. Sarmiento

The relationship between adherence and benefit for those prescribed continuous positive airway pressure (CPAP) devices is clear. However, a Medicare-reimbursement rule that demands adherence blind to circumstances appears to be denying access to many low-income patients, according to an analysis delivered at the annual health policy and advocacy conference sponsored by the American College of Chest Physicians.

Over the past several years, adherence to CPAP has improved substantially following a series of studies that demonstrated the device must be used at least 4 hours per night to achieve improved outcomes. Medicare defines adherence as using the device more than 4 hours per night for 70% of nights (21 nights) during a consecutive 30-day period any time in the first 3 months of initial usage.

However, the studies that show improved adherence show a lag among those in the lowest income quartile, according to Sairam Parthasarathy, MD, director of the Center for Sleep and Circadian Sciences at the University of Arizona, Tucson.

When patients are followed for a year after being prescribed CPAP, the lag for the low-income patients is not seen immediately. Rather, adherence studies show a steady climb in adherence in all income groups initially, but ”right at 90 days there is a marked change,” said Dr. Parthasarathy.

This change happens to coincide with Medicare policy that denies reimbursement for CPAP after 90 days if patients are not using CPAP at least 4 hours per night, which is the threshold associated with benefit.

The correlation between this policy and income disparity is “observational” rather than proven, but Dr. Parthasarathy is confident it is valid. He believes it is a prime example of a health inequity driven by poorly conceived policy.

“The 90-day rule needs to go,” he said, calling the choice of threshold “man-made.” He added: “This is the only disease condition for which a therapy is withheld if it is not used according to some magical threshold. I cannot think of a more draconian policy.”

In an effort to illustrate the problem, he likened this policy to withholding insulin in a diabetes patient judged nonadherent because of a persistently elevated Hb1Ac.

At 90 days, adherence rates remain at a relatively early point in their upwards trajectory in all income groups. One year later, adherence rates are more than twice as high in the highest income relative to the lowest quartile and approaching twofold greater in quartiles 2 and 3.

“It takes time to get used to these devices,” Dr. Parthasarathy explained. Given studies demonstrating that “more is better” with CPAP, whether measured by sleep scales or quality of life, Dr. Parthasarathy advocates strategies to improve adherence, but he questioned an approach that penalizes low-income patients for a definition of nonadherence at an arbitrary point in time. He suggested it is just one example of health policies that ultimately penalize individuals with lower incomes.

“There are millions of dollars spent every year on understanding the genetics of disease, but the biggest influence on how long you live is the ZIP code of where you live,” said Dr. Parthasarathy, referring to ZIP codes as a surrogate for socioeconomic status.

This is not to imply, however, that genetics are irrelevant, Dr. Parthasarathy said. He pointed to data linking genetic traits that determine melanin levels and circadian rhythms. He noted one genotype associated with later bedtimes that is more commonly found in African-Americans and Hispanics. This has relevance to a variety of sleep disorders and other health conditions, but it might serve as a fundamental disadvantage for children with this genotype, Dr. Parthasarathy maintained. He cited a study conducted at his center that found Hispanic children sleep on average 30 minutes less than White children (Sleep Med 2016;18:61-6). The reason was simple. Hispanic children went to bed 30 minutes later but rose at the same time.

The later bedtimes and reduced sleep could potentially be one obstacle among many, such as the need for lower-income patients to hold several jobs, that prevent these patients from becoming accustomed to CPAP at the same speed as wealthier patients, according to Dr. Parthasarathy.

The current Medicare policy that withholds CPAP on the basis of a single definition of nonadherence appears to lead directly to an inequity in treatment of sleep apnea, he maintained. Dr. Parthasarathy, who was a coauthor of a recently published paper on addressing disparities in sleep health (Chest 2021;159:1232-40), described this issue as part of a larger problem of the failure to deliver health care that is sensitive to the cultural and racial differences underlying these inequities.

Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System, agreed. “This type of issue is exactly what our committee would like to address,” said Dr. Sarmiento, a member of the CHEST Health Policy and Advocacy Committee and the moderator of the session in which Dr. Parthasarathy presented his data.

Courtesy Dr. Sarmiento

The relationship between adherence and benefit for those prescribed continuous positive airway pressure (CPAP) devices is clear. However, a Medicare-reimbursement rule that demands adherence blind to circumstances appears to be denying access to many low-income patients, according to an analysis delivered at the annual health policy and advocacy conference sponsored by the American College of Chest Physicians.

Over the past several years, adherence to CPAP has improved substantially following a series of studies that demonstrated the device must be used at least 4 hours per night to achieve improved outcomes. Medicare defines adherence as using the device more than 4 hours per night for 70% of nights (21 nights) during a consecutive 30-day period any time in the first 3 months of initial usage.

However, the studies that show improved adherence show a lag among those in the lowest income quartile, according to Sairam Parthasarathy, MD, director of the Center for Sleep and Circadian Sciences at the University of Arizona, Tucson.

When patients are followed for a year after being prescribed CPAP, the lag for the low-income patients is not seen immediately. Rather, adherence studies show a steady climb in adherence in all income groups initially, but ”right at 90 days there is a marked change,” said Dr. Parthasarathy.

This change happens to coincide with Medicare policy that denies reimbursement for CPAP after 90 days if patients are not using CPAP at least 4 hours per night, which is the threshold associated with benefit.

The correlation between this policy and income disparity is “observational” rather than proven, but Dr. Parthasarathy is confident it is valid. He believes it is a prime example of a health inequity driven by poorly conceived policy.

“The 90-day rule needs to go,” he said, calling the choice of threshold “man-made.” He added: “This is the only disease condition for which a therapy is withheld if it is not used according to some magical threshold. I cannot think of a more draconian policy.”

In an effort to illustrate the problem, he likened this policy to withholding insulin in a diabetes patient judged nonadherent because of a persistently elevated Hb1Ac.

At 90 days, adherence rates remain at a relatively early point in their upwards trajectory in all income groups. One year later, adherence rates are more than twice as high in the highest income relative to the lowest quartile and approaching twofold greater in quartiles 2 and 3.

“It takes time to get used to these devices,” Dr. Parthasarathy explained. Given studies demonstrating that “more is better” with CPAP, whether measured by sleep scales or quality of life, Dr. Parthasarathy advocates strategies to improve adherence, but he questioned an approach that penalizes low-income patients for a definition of nonadherence at an arbitrary point in time. He suggested it is just one example of health policies that ultimately penalize individuals with lower incomes.

“There are millions of dollars spent every year on understanding the genetics of disease, but the biggest influence on how long you live is the ZIP code of where you live,” said Dr. Parthasarathy, referring to ZIP codes as a surrogate for socioeconomic status.

This is not to imply, however, that genetics are irrelevant, Dr. Parthasarathy said. He pointed to data linking genetic traits that determine melanin levels and circadian rhythms. He noted one genotype associated with later bedtimes that is more commonly found in African-Americans and Hispanics. This has relevance to a variety of sleep disorders and other health conditions, but it might serve as a fundamental disadvantage for children with this genotype, Dr. Parthasarathy maintained. He cited a study conducted at his center that found Hispanic children sleep on average 30 minutes less than White children (Sleep Med 2016;18:61-6). The reason was simple. Hispanic children went to bed 30 minutes later but rose at the same time.

The later bedtimes and reduced sleep could potentially be one obstacle among many, such as the need for lower-income patients to hold several jobs, that prevent these patients from becoming accustomed to CPAP at the same speed as wealthier patients, according to Dr. Parthasarathy.

The current Medicare policy that withholds CPAP on the basis of a single definition of nonadherence appears to lead directly to an inequity in treatment of sleep apnea, he maintained. Dr. Parthasarathy, who was a coauthor of a recently published paper on addressing disparities in sleep health (Chest 2021;159:1232-40), described this issue as part of a larger problem of the failure to deliver health care that is sensitive to the cultural and racial differences underlying these inequities.

Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System, agreed. “This type of issue is exactly what our committee would like to address,” said Dr. Sarmiento, a member of the CHEST Health Policy and Advocacy Committee and the moderator of the session in which Dr. Parthasarathy presented his data.

Courtesy Dr. Sarmiento

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.

Iuliia Mikhalitskaia/Getty Images

“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.

The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.

“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”

She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”

Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.

Follow-up analysis

For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.

“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”

Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.

dbrunk@mdedge.com

One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.

Iuliia Mikhalitskaia/Getty Images

“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.

The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.

“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”

She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”

Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.

Follow-up analysis

For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.

“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”

Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.

dbrunk@mdedge.com

One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.

Iuliia Mikhalitskaia/Getty Images

“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.

The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.

“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”

She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”

Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.

Follow-up analysis

For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.

“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”

Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.

dbrunk@mdedge.com

A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.

The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).

However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).

“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.

“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”

The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.

The new survey, which included 153 women and 118 men, was conducted in 2020.

Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).

The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.

The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.

Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.

Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.

However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”

That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.

Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.

ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.

In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.

Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
 

Academia has a problem

To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.

Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.

Most of the respondents (62%) were from academia.

“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.

“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.

A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
 

Harassment from patients/families also tallied

The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).

As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.

And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.

Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.

“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.

“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”

The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.

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

A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.

The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).

However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).

“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.

“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”

The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.

The new survey, which included 153 women and 118 men, was conducted in 2020.

Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).

The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.

The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.

Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.

Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.

However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”

That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.

Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.

ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.

In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.

Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
 

Academia has a problem

To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.

Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.

Most of the respondents (62%) were from academia.

“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.

“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.

A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
 

Harassment from patients/families also tallied

The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).

As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.

And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.

Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.

“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.

“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”

The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.

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

A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.

The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).

However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).

“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.

“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”

The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.

The new survey, which included 153 women and 118 men, was conducted in 2020.

Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).

The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.

The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.

Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.

Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.

However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”

That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.

Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.

ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.

In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.

Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
 

Academia has a problem

To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.

Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.

Most of the respondents (62%) were from academia.

“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.

“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.

A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
 

Harassment from patients/families also tallied

The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).

As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.

And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.

Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.

“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.

“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”

The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.

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

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.

Fuse/Thinkstock

“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.

Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.

The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).

However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.

These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.

The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).

“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
 

Women especially benefit from red meat reduction

The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.

“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.

The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.

The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.

Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.

Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.

The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.

Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.

His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.

“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
 

Building on previous experience

The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.

Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.

“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
 

Study details

CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.

The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.

In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.

In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
 

Surgical results

In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.

Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.

Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).

The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.

Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.

Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).

Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.

Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.

Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
 

Awaiting survival

Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.

The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.

The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.

Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.

His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.

“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
 

Building on previous experience

The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.

Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.

“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
 

Study details

CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.

The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.

In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.

In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
 

Surgical results

In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.

Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.

Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).

The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.

Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.

Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).

Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.

Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.

Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
 

Awaiting survival

Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.

The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.

The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.

Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.

His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.

“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
 

Building on previous experience

The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.

Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.

Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.

“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
 

Study details

CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.

The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.

In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.

In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
 

Surgical results

In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.

Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.

Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).

The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.

Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.

Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).

Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.

Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.

Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
 

Awaiting survival

Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.

The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.

A new immunotherapy, toripalimab, has the potential to change practice in the treatment of nasopharyngeal carcinoma (NPC), say experts.

The drug is a monoclonal antibody that blocks programmed cell death protein 1 (PD-1), developed in China and recently approved there for the third-line treatment of NPC, among other indications. The U.S. Food and Drug Administration has granted it a breakthrough therapy designation for recurrent/metastatic NPC, as well as fast-track and orphan drug status for other tumor types.

New results show that when toripalimab was added onto chemotherapy with gemcitabine and cisplatin in the first line for recurrent or metastatic nasopharyngeal carcinoma, there was a significant improvement in both  progression-free survival and overall survival.

The results come from the phase 3 trial dubbed JUPITER-02 and will be presented at the plenary session of the American Society of Clinical Oncology annual meeting this Sunday; some details were released earlier at a press briefing

The trial randomly assigned 146 patients to toripalimab and 143 to placebo on a background of gemcitabine and cisplatin, the current standard of care for recurrent/metastatic NPC.

Median progression-free survival (PFS) was 11.7 months with toripalimab vs. 8 months with placebo, a significant improvement (hazard ratio, 0.52; 95% confidence interval, 0.36-0.74. P = .0003). Overall survival was not mature at reporting but favored toripalimab with 25 deaths versus 39 in the placebo group, a 40% risk reduction (P = .0462).

The results “support the use of toripalimab in combination with [gemcitabine and cisplatin] as a new standard of care for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma,” said lead investigator and medical oncologist Rui-Hua Xu, MD, PhD, of the Sun Yat-sen University Cancer Center in Guangzhou, China.
 

Potential to change practice

The significance of the study is that it used immunotherapy in the first-line setting for NPC instead of the second line where it’s frequently used today, commented Jared Weiss, MD, an associate professor of oncology and a head and neck cancer specialist at the University of North Carolina, Chapel Hill.

If FDA approves toripalimab for the indication, it “would change [first-line] standard of care to the triplet regimen,” he said in an interview.   

The discussant for this presentation, Julie Gralow, MD, agreed. “This is one of the first studies in metastatic or recurrent NPC to show a benefit” for combining a PD-1 inhibitor with chemotherapy.

“With FDA approval, these findings should prove practice-changing,” said Dr. Gralow, a professor of breast medical oncology at the University of Washington, Seattle, and ASCO’s chief medical officer.

Toripalimab, dosed at 240 mg in the trial, or placebo were administered with gemcitabine and cisplatin every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance every 3 weeks until disease progression, intolerable toxicity, or completion of 2 years of treatment.

The overall response rate was 77.4% with toripalimab and 66.4% with placebo, and the median duration of response in the toripalimab group was 10 months vs. 5.7 months with placebo.

One-year PFS was 49.4% with toripalimab versus 27.9% with placebo; improved PFS was observed with toripalimab across PD-L1 subgroups.

Grade 3 or worse adverse events occurred in slightly less than 90% of both groups, with fatal adverse events occurring in slightly less than 3% in both.

Adverse events leading to discontinuation occurred in 7.5% of the study group and 4.9% on placebo. As expected with immunotherapy, immune-related adverse events such as hypothyroidism were more common with toripalimab (39.7% vs. 18.9%), as were grade 3 or worse immune-related adverse events (7.5% vs. 0.7%).

At interim analysis in May 2020, the median duration treatment was 39 weeks in the toripalimab group and 36 weeks in the placebo group.

The trial was conducted in China, Taiwan, and Singapore.

JUPITER-02 was funded by Shanghai Junshi Bioscience. Investigator disclosures weren’t reported. Dr. Weiss said he had no relevant disclosures. Dr. Gralow is an advisor for a number of companies, including Genentech, Novartis, and Roche.

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

A new immunotherapy, toripalimab, has the potential to change practice in the treatment of nasopharyngeal carcinoma (NPC), say experts.

The drug is a monoclonal antibody that blocks programmed cell death protein 1 (PD-1), developed in China and recently approved there for the third-line treatment of NPC, among other indications. The U.S. Food and Drug Administration has granted it a breakthrough therapy designation for recurrent/metastatic NPC, as well as fast-track and orphan drug status for other tumor types.

New results show that when toripalimab was added onto chemotherapy with gemcitabine and cisplatin in the first line for recurrent or metastatic nasopharyngeal carcinoma, there was a significant improvement in both  progression-free survival and overall survival.

The results come from the phase 3 trial dubbed JUPITER-02 and will be presented at the plenary session of the American Society of Clinical Oncology annual meeting this Sunday; some details were released earlier at a press briefing

The trial randomly assigned 146 patients to toripalimab and 143 to placebo on a background of gemcitabine and cisplatin, the current standard of care for recurrent/metastatic NPC.

Median progression-free survival (PFS) was 11.7 months with toripalimab vs. 8 months with placebo, a significant improvement (hazard ratio, 0.52; 95% confidence interval, 0.36-0.74. P = .0003). Overall survival was not mature at reporting but favored toripalimab with 25 deaths versus 39 in the placebo group, a 40% risk reduction (P = .0462).

The results “support the use of toripalimab in combination with [gemcitabine and cisplatin] as a new standard of care for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma,” said lead investigator and medical oncologist Rui-Hua Xu, MD, PhD, of the Sun Yat-sen University Cancer Center in Guangzhou, China.
 

Potential to change practice

The significance of the study is that it used immunotherapy in the first-line setting for NPC instead of the second line where it’s frequently used today, commented Jared Weiss, MD, an associate professor of oncology and a head and neck cancer specialist at the University of North Carolina, Chapel Hill.

If FDA approves toripalimab for the indication, it “would change [first-line] standard of care to the triplet regimen,” he said in an interview.   

The discussant for this presentation, Julie Gralow, MD, agreed. “This is one of the first studies in metastatic or recurrent NPC to show a benefit” for combining a PD-1 inhibitor with chemotherapy.

“With FDA approval, these findings should prove practice-changing,” said Dr. Gralow, a professor of breast medical oncology at the University of Washington, Seattle, and ASCO’s chief medical officer.

Toripalimab, dosed at 240 mg in the trial, or placebo were administered with gemcitabine and cisplatin every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance every 3 weeks until disease progression, intolerable toxicity, or completion of 2 years of treatment.

The overall response rate was 77.4% with toripalimab and 66.4% with placebo, and the median duration of response in the toripalimab group was 10 months vs. 5.7 months with placebo.

One-year PFS was 49.4% with toripalimab versus 27.9% with placebo; improved PFS was observed with toripalimab across PD-L1 subgroups.

Grade 3 or worse adverse events occurred in slightly less than 90% of both groups, with fatal adverse events occurring in slightly less than 3% in both.

Adverse events leading to discontinuation occurred in 7.5% of the study group and 4.9% on placebo. As expected with immunotherapy, immune-related adverse events such as hypothyroidism were more common with toripalimab (39.7% vs. 18.9%), as were grade 3 or worse immune-related adverse events (7.5% vs. 0.7%).

At interim analysis in May 2020, the median duration treatment was 39 weeks in the toripalimab group and 36 weeks in the placebo group.

The trial was conducted in China, Taiwan, and Singapore.

JUPITER-02 was funded by Shanghai Junshi Bioscience. Investigator disclosures weren’t reported. Dr. Weiss said he had no relevant disclosures. Dr. Gralow is an advisor for a number of companies, including Genentech, Novartis, and Roche.

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

A new immunotherapy, toripalimab, has the potential to change practice in the treatment of nasopharyngeal carcinoma (NPC), say experts.

The drug is a monoclonal antibody that blocks programmed cell death protein 1 (PD-1), developed in China and recently approved there for the third-line treatment of NPC, among other indications. The U.S. Food and Drug Administration has granted it a breakthrough therapy designation for recurrent/metastatic NPC, as well as fast-track and orphan drug status for other tumor types.

New results show that when toripalimab was added onto chemotherapy with gemcitabine and cisplatin in the first line for recurrent or metastatic nasopharyngeal carcinoma, there was a significant improvement in both  progression-free survival and overall survival.

The results come from the phase 3 trial dubbed JUPITER-02 and will be presented at the plenary session of the American Society of Clinical Oncology annual meeting this Sunday; some details were released earlier at a press briefing

The trial randomly assigned 146 patients to toripalimab and 143 to placebo on a background of gemcitabine and cisplatin, the current standard of care for recurrent/metastatic NPC.

Median progression-free survival (PFS) was 11.7 months with toripalimab vs. 8 months with placebo, a significant improvement (hazard ratio, 0.52; 95% confidence interval, 0.36-0.74. P = .0003). Overall survival was not mature at reporting but favored toripalimab with 25 deaths versus 39 in the placebo group, a 40% risk reduction (P = .0462).

The results “support the use of toripalimab in combination with [gemcitabine and cisplatin] as a new standard of care for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma,” said lead investigator and medical oncologist Rui-Hua Xu, MD, PhD, of the Sun Yat-sen University Cancer Center in Guangzhou, China.
 

Potential to change practice

The significance of the study is that it used immunotherapy in the first-line setting for NPC instead of the second line where it’s frequently used today, commented Jared Weiss, MD, an associate professor of oncology and a head and neck cancer specialist at the University of North Carolina, Chapel Hill.

If FDA approves toripalimab for the indication, it “would change [first-line] standard of care to the triplet regimen,” he said in an interview.   

The discussant for this presentation, Julie Gralow, MD, agreed. “This is one of the first studies in metastatic or recurrent NPC to show a benefit” for combining a PD-1 inhibitor with chemotherapy.

“With FDA approval, these findings should prove practice-changing,” said Dr. Gralow, a professor of breast medical oncology at the University of Washington, Seattle, and ASCO’s chief medical officer.

Toripalimab, dosed at 240 mg in the trial, or placebo were administered with gemcitabine and cisplatin every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance every 3 weeks until disease progression, intolerable toxicity, or completion of 2 years of treatment.

The overall response rate was 77.4% with toripalimab and 66.4% with placebo, and the median duration of response in the toripalimab group was 10 months vs. 5.7 months with placebo.

One-year PFS was 49.4% with toripalimab versus 27.9% with placebo; improved PFS was observed with toripalimab across PD-L1 subgroups.

Grade 3 or worse adverse events occurred in slightly less than 90% of both groups, with fatal adverse events occurring in slightly less than 3% in both.

Adverse events leading to discontinuation occurred in 7.5% of the study group and 4.9% on placebo. As expected with immunotherapy, immune-related adverse events such as hypothyroidism were more common with toripalimab (39.7% vs. 18.9%), as were grade 3 or worse immune-related adverse events (7.5% vs. 0.7%).

At interim analysis in May 2020, the median duration treatment was 39 weeks in the toripalimab group and 36 weeks in the placebo group.

The trial was conducted in China, Taiwan, and Singapore.

JUPITER-02 was funded by Shanghai Junshi Bioscience. Investigator disclosures weren’t reported. Dr. Weiss said he had no relevant disclosures. Dr. Gralow is an advisor for a number of companies, including Genentech, Novartis, and Roche.

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