Few ever see this side of cancer care. Our cameras go behind the scenes as a surgical oncologist faces a crucial moment in the OR in this first episode of a new video series, The Oncologists.

Medscape Oncology © 2021 WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.

Few ever see this side of cancer care. Our cameras go behind the scenes as a surgical oncologist faces a crucial moment in the OR in this first episode of a new video series, The Oncologists.

Medscape Oncology © 2021 WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.

Few ever see this side of cancer care. Our cameras go behind the scenes as a surgical oncologist faces a crucial moment in the OR in this first episode of a new video series, The Oncologists.

Medscape Oncology © 2021 WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.

Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.

A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.

This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.

There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.

HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”

“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.

But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.

“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.

He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
 

Existing data on HPD

HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.

In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.

The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.

That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).

Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.

In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.

However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.

Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.

Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.

Both groups of authors emphasize the urgent need for prospective studies.

It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.

The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.

The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.

Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.

“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
 

Steps for solving the HPD mystery

“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”

Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.

“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”

Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.

Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.

The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.

“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.

“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.

Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.

He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.

“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
 

Current treatment decision-making

Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.

For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.

“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.

Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.

Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).

“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”

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

Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.

A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.

This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.

There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.

HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”

“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.

But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.

“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.

He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
 

Existing data on HPD

HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.

In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.

The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.

That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).

Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.

In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.

However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.

Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.

Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.

Both groups of authors emphasize the urgent need for prospective studies.

It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.

The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.

The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.

Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.

“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
 

Steps for solving the HPD mystery

“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”

Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.

“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”

Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.

Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.

The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.

“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.

“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.

Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.

He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.

“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
 

Current treatment decision-making

Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.

For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.

“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.

Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.

Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).

“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”

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

Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.

A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.

This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.

There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.

HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”

“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.

But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.

“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.

He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
 

Existing data on HPD

HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.

In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.

The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.

That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).

Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.

In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.

However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.

Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.

Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.

Both groups of authors emphasize the urgent need for prospective studies.

It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.

The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.

The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.

Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.

“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
 

Steps for solving the HPD mystery

“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”

Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.

“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”

Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.

Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.

The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.

“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.

“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.

Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.

He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.

“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
 

Current treatment decision-making

Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.

For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.

“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.

Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.

Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).

“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”

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

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

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

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

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

COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.

Courtesy Bill Branson/National Cancer Institute

Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.

In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.

Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.

In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
 

Loss of control

Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.

To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.

In the first assessment, conducted in April 2020, the researchers assessed 59 outpatients with EDs and 43 unaffected hospital staff and their acquaintances. The second group served as the control group.

Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.

The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).

In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
 

Clinical implications

A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.

Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.

These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.

These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.

In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.

They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.

Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
 

Bulimia patients more vulnerable

After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.

All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.

The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).

Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.

In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).

“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”

The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.

In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
 

Evidence of recovery

Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.

“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.

“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.

“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.

The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”

The study authors and Dr. Spiegel reported no relevant financial relationships.

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

Background: A pulmonary embolism can be considered ruled out if patients have a low C-PTP for PE and a D-dimer level of less than 500 ng/mL. However, this occurs in approximately 30% of outpatients only. By increasing the D-dimer threshold used to define a negative test to 1,000 ng/mL in patients with a low C-PTP, we might be able to rule out a larger segment of patients and avoid chest imaging.

Study design: Prospective study.

Setting: University-based clinical centers in Canada.

Synopsis: This study enrolled 2,017 patients presenting with symptoms of PE. The Wells’ criteria was used to categorize the patient’s C-PTP as low (0-4.0), moderate (4.5-6.0), or high (6.5 or more). Patients with a low or moderate C-PTP had a D dimer drawn. Those with a low C-PTP and D dimer of less than 1,000 ng/mL or moderate C-PTP and a D dimer of less than 500 ng/mL underwent no further testing. Outcomes were assessed at 90 days. Of the 1,325 patients with a low C-PTP or moderate C-PTP and a negative D-dimer test (less than 1,000 or 500 ng/mL, respectively), none had venous thromboembolism during follow-up (95% confidence interval, 0.00-0.29). This strategy resulted in the use of chest imaging in only 34.3% of patients versus 51.9% using the prior criteria of a D-dimer level of less than 500 ng/mL (difference, –17.6 percentage points; 95% CI, −19.2 to −15.9). One limitation of the study is that almost all patients enrolled were outpatients (only one inpatient).

Bottom line: A combination of a low C-PTP and a D-dimer level of less than 1,000 ng/mL identified a group of patients at low risk for pulmonary embolism during follow-up.

Citation: Kearon C et al. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med 2019 Nov 28;381:2125-34.

Dr. Santa is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

Background: A pulmonary embolism can be considered ruled out if patients have a low C-PTP for PE and a D-dimer level of less than 500 ng/mL. However, this occurs in approximately 30% of outpatients only. By increasing the D-dimer threshold used to define a negative test to 1,000 ng/mL in patients with a low C-PTP, we might be able to rule out a larger segment of patients and avoid chest imaging.

Study design: Prospective study.

Setting: University-based clinical centers in Canada.

Synopsis: This study enrolled 2,017 patients presenting with symptoms of PE. The Wells’ criteria was used to categorize the patient’s C-PTP as low (0-4.0), moderate (4.5-6.0), or high (6.5 or more). Patients with a low or moderate C-PTP had a D dimer drawn. Those with a low C-PTP and D dimer of less than 1,000 ng/mL or moderate C-PTP and a D dimer of less than 500 ng/mL underwent no further testing. Outcomes were assessed at 90 days. Of the 1,325 patients with a low C-PTP or moderate C-PTP and a negative D-dimer test (less than 1,000 or 500 ng/mL, respectively), none had venous thromboembolism during follow-up (95% confidence interval, 0.00-0.29). This strategy resulted in the use of chest imaging in only 34.3% of patients versus 51.9% using the prior criteria of a D-dimer level of less than 500 ng/mL (difference, –17.6 percentage points; 95% CI, −19.2 to −15.9). One limitation of the study is that almost all patients enrolled were outpatients (only one inpatient).

Bottom line: A combination of a low C-PTP and a D-dimer level of less than 1,000 ng/mL identified a group of patients at low risk for pulmonary embolism during follow-up.

Citation: Kearon C et al. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med 2019 Nov 28;381:2125-34.

Dr. Santa is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

Background: A pulmonary embolism can be considered ruled out if patients have a low C-PTP for PE and a D-dimer level of less than 500 ng/mL. However, this occurs in approximately 30% of outpatients only. By increasing the D-dimer threshold used to define a negative test to 1,000 ng/mL in patients with a low C-PTP, we might be able to rule out a larger segment of patients and avoid chest imaging.

Study design: Prospective study.

Setting: University-based clinical centers in Canada.

Synopsis: This study enrolled 2,017 patients presenting with symptoms of PE. The Wells’ criteria was used to categorize the patient’s C-PTP as low (0-4.0), moderate (4.5-6.0), or high (6.5 or more). Patients with a low or moderate C-PTP had a D dimer drawn. Those with a low C-PTP and D dimer of less than 1,000 ng/mL or moderate C-PTP and a D dimer of less than 500 ng/mL underwent no further testing. Outcomes were assessed at 90 days. Of the 1,325 patients with a low C-PTP or moderate C-PTP and a negative D-dimer test (less than 1,000 or 500 ng/mL, respectively), none had venous thromboembolism during follow-up (95% confidence interval, 0.00-0.29). This strategy resulted in the use of chest imaging in only 34.3% of patients versus 51.9% using the prior criteria of a D-dimer level of less than 500 ng/mL (difference, –17.6 percentage points; 95% CI, −19.2 to −15.9). One limitation of the study is that almost all patients enrolled were outpatients (only one inpatient).

Bottom line: A combination of a low C-PTP and a D-dimer level of less than 1,000 ng/mL identified a group of patients at low risk for pulmonary embolism during follow-up.

Citation: Kearon C et al. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med 2019 Nov 28;381:2125-34.

Dr. Santa is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.

A newly released report is offering guidance concerning rare conditions associated with COVID-19 as well as vaccines against the virus.

The report was released April 29, 2021, by the American Heart Association/American Stroke Association Stroke Council Leadership in answer to the decision April 23 by the Centers for Disease Control and Prevention and the Food and Drug Administration to lift an earlier “pause” in administration of the Johnson & Johnson (Janssen) vaccine.

That pause had been put in place after reports were received of a possible association between the J&J vaccine and cerebral venous sinus thrombosis (CVST) and thrombosis-thrombocytopenia syndrome (TTS, blood clots plus low blood platelets). CVST and TTS were also linked to patients in Europe and Canada who received the AstraZeneca COVID-19 vaccine.

However, the new report noted that these conditions are very rare.

“The risk of CVST due to infection with COVID-19 is 8-10 times higher than the risk of CVST after receiving a COVID-19 vaccine,” lead author Karen L. Furie, MD, chair of the department of neurology at Brown University, Providence, R.I., said in a press release.

“The public can be reassured by the CDC’s and FDA’s investigation and these statistics – the likelihood of developing CVST after a COVID-19 vaccine is extremely low,” said Dr. Furie, adding that the authors “urge all adults to receive any of the approved COVID-19 vaccines.”

The new guidance, which was published online April 29, 2021, in Stroke, discusses signs and symptoms of CVST and TTS, as well as vaccine-induced immune thrombotic thrombocytopenia (VITT). It also recommends best options for treating these conditions.
 

Assessing 81 million patients

In their analysis, the investigators assessed a database of 59 health care organizations and 81 million patients, 98% of whom were in the United States.

Of almost 514,000 patients diagnosed with COVID-19 between January 2020 and March 2021, 20 also received a diagnosis of CVST.

Among about 490,000 adults who received either the Pfizer or Moderna vaccines, there were no diagnosed cases of thrombocytopenia.

Dr. Furie reiterated that CVST blood clots “are very rare adverse events,” but recommended that any patient in the ED with a suspected clot should be screened immediately to determine if they received a COVID vaccine during the previous few weeks.

For those who have recently received the COVID-19 vaccine, a suspected clot should be treated with nonheparin anticoagulants, Dr. Furie said.

“No heparin products in any dose should be given for suspected CVST, TTS, or VITT. With the right treatment, most patients can have a full recovery,” she added. The report includes additional, detailed treatment recommendations if one of these conditions are suspected. 
 

Rare events

The authors noted that cases of TTS/VITT occurred up to 2.5 weeks after receiving the J&J vaccine in the United States and up to 3.5 weeks after receiving the AstraZeneca vaccine in Europe.

An April 23 report from the CDC and FDA noted that, out of almost 7 million adults who received the J&J vaccine, the agencies investigated only 15 reported cases of TTS.

An April 7 report from the European Medicines Agency noted that, out of more than 25 million people who received the AstraZeneca vaccine in the European Union, it found 62 cases of CVST.

A statement put out by the American Heart Association/American Stroke Association urges “everyone to receive a COVID-19 vaccine” as soon as possible.

“We are confident the benefits of vaccination far exceed the very small, rare risks,” the organizations said. “The risks of vaccination are also far smaller than the risk of COVID-19 and its potentially fatal consequences.”

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

A newly released report is offering guidance concerning rare conditions associated with COVID-19 as well as vaccines against the virus.

The report was released April 29, 2021, by the American Heart Association/American Stroke Association Stroke Council Leadership in answer to the decision April 23 by the Centers for Disease Control and Prevention and the Food and Drug Administration to lift an earlier “pause” in administration of the Johnson & Johnson (Janssen) vaccine.

That pause had been put in place after reports were received of a possible association between the J&J vaccine and cerebral venous sinus thrombosis (CVST) and thrombosis-thrombocytopenia syndrome (TTS, blood clots plus low blood platelets). CVST and TTS were also linked to patients in Europe and Canada who received the AstraZeneca COVID-19 vaccine.

However, the new report noted that these conditions are very rare.

“The risk of CVST due to infection with COVID-19 is 8-10 times higher than the risk of CVST after receiving a COVID-19 vaccine,” lead author Karen L. Furie, MD, chair of the department of neurology at Brown University, Providence, R.I., said in a press release.

“The public can be reassured by the CDC’s and FDA’s investigation and these statistics – the likelihood of developing CVST after a COVID-19 vaccine is extremely low,” said Dr. Furie, adding that the authors “urge all adults to receive any of the approved COVID-19 vaccines.”

The new guidance, which was published online April 29, 2021, in Stroke, discusses signs and symptoms of CVST and TTS, as well as vaccine-induced immune thrombotic thrombocytopenia (VITT). It also recommends best options for treating these conditions.
 

Assessing 81 million patients

In their analysis, the investigators assessed a database of 59 health care organizations and 81 million patients, 98% of whom were in the United States.

Of almost 514,000 patients diagnosed with COVID-19 between January 2020 and March 2021, 20 also received a diagnosis of CVST.

Among about 490,000 adults who received either the Pfizer or Moderna vaccines, there were no diagnosed cases of thrombocytopenia.

Dr. Furie reiterated that CVST blood clots “are very rare adverse events,” but recommended that any patient in the ED with a suspected clot should be screened immediately to determine if they received a COVID vaccine during the previous few weeks.

For those who have recently received the COVID-19 vaccine, a suspected clot should be treated with nonheparin anticoagulants, Dr. Furie said.

“No heparin products in any dose should be given for suspected CVST, TTS, or VITT. With the right treatment, most patients can have a full recovery,” she added. The report includes additional, detailed treatment recommendations if one of these conditions are suspected. 
 

Rare events

The authors noted that cases of TTS/VITT occurred up to 2.5 weeks after receiving the J&J vaccine in the United States and up to 3.5 weeks after receiving the AstraZeneca vaccine in Europe.

An April 23 report from the CDC and FDA noted that, out of almost 7 million adults who received the J&J vaccine, the agencies investigated only 15 reported cases of TTS.

An April 7 report from the European Medicines Agency noted that, out of more than 25 million people who received the AstraZeneca vaccine in the European Union, it found 62 cases of CVST.

A statement put out by the American Heart Association/American Stroke Association urges “everyone to receive a COVID-19 vaccine” as soon as possible.

“We are confident the benefits of vaccination far exceed the very small, rare risks,” the organizations said. “The risks of vaccination are also far smaller than the risk of COVID-19 and its potentially fatal consequences.”

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

A newly released report is offering guidance concerning rare conditions associated with COVID-19 as well as vaccines against the virus.

The report was released April 29, 2021, by the American Heart Association/American Stroke Association Stroke Council Leadership in answer to the decision April 23 by the Centers for Disease Control and Prevention and the Food and Drug Administration to lift an earlier “pause” in administration of the Johnson & Johnson (Janssen) vaccine.

That pause had been put in place after reports were received of a possible association between the J&J vaccine and cerebral venous sinus thrombosis (CVST) and thrombosis-thrombocytopenia syndrome (TTS, blood clots plus low blood platelets). CVST and TTS were also linked to patients in Europe and Canada who received the AstraZeneca COVID-19 vaccine.

However, the new report noted that these conditions are very rare.

“The risk of CVST due to infection with COVID-19 is 8-10 times higher than the risk of CVST after receiving a COVID-19 vaccine,” lead author Karen L. Furie, MD, chair of the department of neurology at Brown University, Providence, R.I., said in a press release.

“The public can be reassured by the CDC’s and FDA’s investigation and these statistics – the likelihood of developing CVST after a COVID-19 vaccine is extremely low,” said Dr. Furie, adding that the authors “urge all adults to receive any of the approved COVID-19 vaccines.”

The new guidance, which was published online April 29, 2021, in Stroke, discusses signs and symptoms of CVST and TTS, as well as vaccine-induced immune thrombotic thrombocytopenia (VITT). It also recommends best options for treating these conditions.
 

Assessing 81 million patients

In their analysis, the investigators assessed a database of 59 health care organizations and 81 million patients, 98% of whom were in the United States.

Of almost 514,000 patients diagnosed with COVID-19 between January 2020 and March 2021, 20 also received a diagnosis of CVST.

Among about 490,000 adults who received either the Pfizer or Moderna vaccines, there were no diagnosed cases of thrombocytopenia.

Dr. Furie reiterated that CVST blood clots “are very rare adverse events,” but recommended that any patient in the ED with a suspected clot should be screened immediately to determine if they received a COVID vaccine during the previous few weeks.

For those who have recently received the COVID-19 vaccine, a suspected clot should be treated with nonheparin anticoagulants, Dr. Furie said.

“No heparin products in any dose should be given for suspected CVST, TTS, or VITT. With the right treatment, most patients can have a full recovery,” she added. The report includes additional, detailed treatment recommendations if one of these conditions are suspected. 
 

Rare events

The authors noted that cases of TTS/VITT occurred up to 2.5 weeks after receiving the J&J vaccine in the United States and up to 3.5 weeks after receiving the AstraZeneca vaccine in Europe.

An April 23 report from the CDC and FDA noted that, out of almost 7 million adults who received the J&J vaccine, the agencies investigated only 15 reported cases of TTS.

An April 7 report from the European Medicines Agency noted that, out of more than 25 million people who received the AstraZeneca vaccine in the European Union, it found 62 cases of CVST.

A statement put out by the American Heart Association/American Stroke Association urges “everyone to receive a COVID-19 vaccine” as soon as possible.

“We are confident the benefits of vaccination far exceed the very small, rare risks,” the organizations said. “The risks of vaccination are also far smaller than the risk of COVID-19 and its potentially fatal consequences.”

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

Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.

Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.

“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.

The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.

“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.

Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.

“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.

Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.

“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”

Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.

Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.

Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.

Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.

In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.

“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”

Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.

However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.

The study author and experts disclosed no relevant financial relationships.

Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.

Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.

“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.

The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.

“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.

Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.

“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.

Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.

“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”

Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.

Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.

Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.

Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.

In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.

“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”

Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.

However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.

The study author and experts disclosed no relevant financial relationships.

Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.

Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.

“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.

The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.

“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.

Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.

“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.

Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.

“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”

Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.

Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.

Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.

Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.

In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.

“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”

Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.

However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.

The study author and experts disclosed no relevant financial relationships.

Lobaplatin-based induction plus chemoradiation was as effective as, and safer than, a cisplatin-based regimen in a phase 3 trial of more than 500 patients with advanced nasopharyngeal carcinoma.

The lobaplatin regimen proved to be a “promising alternative regimen to cisplatin-based treatment,” Xing Lv, MD, of Sun Yat-sen University Cancer Centre in Guangzhou, China, and colleagues wrote in The Lancet Oncology.

A lobaplatin-based regimen might be particularly attractive when cisplatin is contraindicated, according to authors of a related editorial.

Given the encouraging results in this trial, lobaplatin might even “overtake carboplatin” in cisplatin-ineligible patients, wrote the editorialists, Stefano Cavalieri, MD, and Lisa Licitra, MD, both of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano in Italy.

“Furthermore, the optimal treatment compliance in patients receiving lobaplatin [in the trial] suggests that this agent might be a good candidate for research into escalation strategies,” the editorialists wrote.
 

Study rationale

Cisplatin-based induction followed by concurrent chemoradiotherapy is a standard treatment option in the United States, recommended by National Comprehensive Cancer Network guidelines for stage II-IVB nasopharyngeal carcinoma.

However, cisplatin is associated with poor treatment compliance due to significant hematologic and nonhematologic side effects. Cisplatin also requires increased hydration for renal protection, increasing the risk of fluid overload.

“Safer and more effective platinum drugs are needed for the treatment of nasopharyngeal carcinoma,” the investigators wrote.

Carboplatin is an alternative available in the United States, but “the evidence supporting equivalence between cisplatin with carboplatin is still controversial” for nasopharyngeal cancer, the editorialists wrote.
 

Study details

The phase 3 study enrolled 502 patients from five hospitals in China. The patients had previously untreated, non-keratinizing stage III–IVB nasopharyngeal carcinoma and a Karnofsky performance status score of at least 70. The study excluded patients older than 60 years of age, and adequate renal, hematologic, and hepatic function were required.

Half of patients (n = 252) were randomized to induction with lobaplatin and fluorouracil for two cycles followed by concurrent therapy with lobaplatin for two cycles plus intensity-modulated radiotherapy. The other half of patients (n = 250) were randomized to cisplatin-fluorouracil induction for two cycles, followed by intensity-modulated radiotherapy plus two cycles of cisplatin.

The investigators opted for two-cycle chemotherapy instead of three cycles after observing good activity and safety with two cycles in a phase 2 trial.

Treatment compliance was better in the lobaplatin arm, with 91% of those patients completing two cycles of concurrent chemotherapy, compared with 84% of patients in the cisplatin arm.

The 5-year progression-free survival rate was 75% in the lobaplatin arm and 75.5% in the cisplatin arm in the intention-to-treat population (P noninferiority = .007).

In the per-protocol population, the 5-year progression-free survival rates were 74.8% with lobaplatin and 76.4% with cisplatin (P noninferiority = .016).

The most common grade 3-4 adverse events were mucositis (41% in the lobaplatin arm and 40% in the cisplatin arm), leukopenia (16% and 23%, respectively), and neutropenia (10% and 24%, respectively).

Grade 1-2 nephrotoxicity, nausea, vomiting, and weight loss were significantly less common with lobaplatin (P < .0001 for all).

Questions about generalizability

The editorialists urged caution about generalizing the study results to a wider population.

Study subjects were younger and had no major comorbidities as well as good renal function, which is not always the case with nasopharyngeal carcinoma. In addition, although antiemesis prophylaxis was the standard of care for the study period (2013-2015), guidelines have since been updated to included more intense premedication, which likely would have reduced nausea, vomiting, weight loss, and possibly nephrotoxicity, especially in the cisplatin group.

Induction chemotherapy consisted of cisplatin and fluorouracil, whereas current standards for induction chemotherapy are cisplatin plus gemcitabine or docetaxel plus cisplatin and fluorouracil, the editorialists noted.

As for the two-cycle approach, it’s known that concomitant chemoradiotherapy with two cycles of cisplatin in head and neck cancer “provides similar outcomes to concomitant chemoradiotherapy with three cycles, but only in cases of accelerated intensity-modulated radiotherapy,” not with the standard fractionation used in the study (30-32 fractions, 5 days per week), the editorialists wrote.

The study was funded by the National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. The investigators and Dr. Cavalieri declared no competing interests. Dr. Licitra disclosed relationships AstraZeneca, Bristol Myers Squibb, and Hoffmann-La Roche.

[email protected]

Lobaplatin-based induction plus chemoradiation was as effective as, and safer than, a cisplatin-based regimen in a phase 3 trial of more than 500 patients with advanced nasopharyngeal carcinoma.

The lobaplatin regimen proved to be a “promising alternative regimen to cisplatin-based treatment,” Xing Lv, MD, of Sun Yat-sen University Cancer Centre in Guangzhou, China, and colleagues wrote in The Lancet Oncology.

A lobaplatin-based regimen might be particularly attractive when cisplatin is contraindicated, according to authors of a related editorial.

Given the encouraging results in this trial, lobaplatin might even “overtake carboplatin” in cisplatin-ineligible patients, wrote the editorialists, Stefano Cavalieri, MD, and Lisa Licitra, MD, both of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano in Italy.

“Furthermore, the optimal treatment compliance in patients receiving lobaplatin [in the trial] suggests that this agent might be a good candidate for research into escalation strategies,” the editorialists wrote.
 

Study rationale

Cisplatin-based induction followed by concurrent chemoradiotherapy is a standard treatment option in the United States, recommended by National Comprehensive Cancer Network guidelines for stage II-IVB nasopharyngeal carcinoma.

However, cisplatin is associated with poor treatment compliance due to significant hematologic and nonhematologic side effects. Cisplatin also requires increased hydration for renal protection, increasing the risk of fluid overload.

“Safer and more effective platinum drugs are needed for the treatment of nasopharyngeal carcinoma,” the investigators wrote.

Carboplatin is an alternative available in the United States, but “the evidence supporting equivalence between cisplatin with carboplatin is still controversial” for nasopharyngeal cancer, the editorialists wrote.
 

Study details

The phase 3 study enrolled 502 patients from five hospitals in China. The patients had previously untreated, non-keratinizing stage III–IVB nasopharyngeal carcinoma and a Karnofsky performance status score of at least 70. The study excluded patients older than 60 years of age, and adequate renal, hematologic, and hepatic function were required.

Half of patients (n = 252) were randomized to induction with lobaplatin and fluorouracil for two cycles followed by concurrent therapy with lobaplatin for two cycles plus intensity-modulated radiotherapy. The other half of patients (n = 250) were randomized to cisplatin-fluorouracil induction for two cycles, followed by intensity-modulated radiotherapy plus two cycles of cisplatin.

The investigators opted for two-cycle chemotherapy instead of three cycles after observing good activity and safety with two cycles in a phase 2 trial.

Treatment compliance was better in the lobaplatin arm, with 91% of those patients completing two cycles of concurrent chemotherapy, compared with 84% of patients in the cisplatin arm.

The 5-year progression-free survival rate was 75% in the lobaplatin arm and 75.5% in the cisplatin arm in the intention-to-treat population (P noninferiority = .007).

In the per-protocol population, the 5-year progression-free survival rates were 74.8% with lobaplatin and 76.4% with cisplatin (P noninferiority = .016).

The most common grade 3-4 adverse events were mucositis (41% in the lobaplatin arm and 40% in the cisplatin arm), leukopenia (16% and 23%, respectively), and neutropenia (10% and 24%, respectively).

Grade 1-2 nephrotoxicity, nausea, vomiting, and weight loss were significantly less common with lobaplatin (P < .0001 for all).

Questions about generalizability

The editorialists urged caution about generalizing the study results to a wider population.

Study subjects were younger and had no major comorbidities as well as good renal function, which is not always the case with nasopharyngeal carcinoma. In addition, although antiemesis prophylaxis was the standard of care for the study period (2013-2015), guidelines have since been updated to included more intense premedication, which likely would have reduced nausea, vomiting, weight loss, and possibly nephrotoxicity, especially in the cisplatin group.

Induction chemotherapy consisted of cisplatin and fluorouracil, whereas current standards for induction chemotherapy are cisplatin plus gemcitabine or docetaxel plus cisplatin and fluorouracil, the editorialists noted.

As for the two-cycle approach, it’s known that concomitant chemoradiotherapy with two cycles of cisplatin in head and neck cancer “provides similar outcomes to concomitant chemoradiotherapy with three cycles, but only in cases of accelerated intensity-modulated radiotherapy,” not with the standard fractionation used in the study (30-32 fractions, 5 days per week), the editorialists wrote.

The study was funded by the National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. The investigators and Dr. Cavalieri declared no competing interests. Dr. Licitra disclosed relationships AstraZeneca, Bristol Myers Squibb, and Hoffmann-La Roche.

[email protected]

Lobaplatin-based induction plus chemoradiation was as effective as, and safer than, a cisplatin-based regimen in a phase 3 trial of more than 500 patients with advanced nasopharyngeal carcinoma.

The lobaplatin regimen proved to be a “promising alternative regimen to cisplatin-based treatment,” Xing Lv, MD, of Sun Yat-sen University Cancer Centre in Guangzhou, China, and colleagues wrote in The Lancet Oncology.

A lobaplatin-based regimen might be particularly attractive when cisplatin is contraindicated, according to authors of a related editorial.

Given the encouraging results in this trial, lobaplatin might even “overtake carboplatin” in cisplatin-ineligible patients, wrote the editorialists, Stefano Cavalieri, MD, and Lisa Licitra, MD, both of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano in Italy.

“Furthermore, the optimal treatment compliance in patients receiving lobaplatin [in the trial] suggests that this agent might be a good candidate for research into escalation strategies,” the editorialists wrote.
 

Study rationale

Cisplatin-based induction followed by concurrent chemoradiotherapy is a standard treatment option in the United States, recommended by National Comprehensive Cancer Network guidelines for stage II-IVB nasopharyngeal carcinoma.

However, cisplatin is associated with poor treatment compliance due to significant hematologic and nonhematologic side effects. Cisplatin also requires increased hydration for renal protection, increasing the risk of fluid overload.

“Safer and more effective platinum drugs are needed for the treatment of nasopharyngeal carcinoma,” the investigators wrote.

Carboplatin is an alternative available in the United States, but “the evidence supporting equivalence between cisplatin with carboplatin is still controversial” for nasopharyngeal cancer, the editorialists wrote.
 

Study details

The phase 3 study enrolled 502 patients from five hospitals in China. The patients had previously untreated, non-keratinizing stage III–IVB nasopharyngeal carcinoma and a Karnofsky performance status score of at least 70. The study excluded patients older than 60 years of age, and adequate renal, hematologic, and hepatic function were required.

Half of patients (n = 252) were randomized to induction with lobaplatin and fluorouracil for two cycles followed by concurrent therapy with lobaplatin for two cycles plus intensity-modulated radiotherapy. The other half of patients (n = 250) were randomized to cisplatin-fluorouracil induction for two cycles, followed by intensity-modulated radiotherapy plus two cycles of cisplatin.

The investigators opted for two-cycle chemotherapy instead of three cycles after observing good activity and safety with two cycles in a phase 2 trial.

Treatment compliance was better in the lobaplatin arm, with 91% of those patients completing two cycles of concurrent chemotherapy, compared with 84% of patients in the cisplatin arm.

The 5-year progression-free survival rate was 75% in the lobaplatin arm and 75.5% in the cisplatin arm in the intention-to-treat population (P noninferiority = .007).

In the per-protocol population, the 5-year progression-free survival rates were 74.8% with lobaplatin and 76.4% with cisplatin (P noninferiority = .016).

The most common grade 3-4 adverse events were mucositis (41% in the lobaplatin arm and 40% in the cisplatin arm), leukopenia (16% and 23%, respectively), and neutropenia (10% and 24%, respectively).

Grade 1-2 nephrotoxicity, nausea, vomiting, and weight loss were significantly less common with lobaplatin (P < .0001 for all).

Questions about generalizability

The editorialists urged caution about generalizing the study results to a wider population.

Study subjects were younger and had no major comorbidities as well as good renal function, which is not always the case with nasopharyngeal carcinoma. In addition, although antiemesis prophylaxis was the standard of care for the study period (2013-2015), guidelines have since been updated to included more intense premedication, which likely would have reduced nausea, vomiting, weight loss, and possibly nephrotoxicity, especially in the cisplatin group.

Induction chemotherapy consisted of cisplatin and fluorouracil, whereas current standards for induction chemotherapy are cisplatin plus gemcitabine or docetaxel plus cisplatin and fluorouracil, the editorialists noted.

As for the two-cycle approach, it’s known that concomitant chemoradiotherapy with two cycles of cisplatin in head and neck cancer “provides similar outcomes to concomitant chemoradiotherapy with three cycles, but only in cases of accelerated intensity-modulated radiotherapy,” not with the standard fractionation used in the study (30-32 fractions, 5 days per week), the editorialists wrote.

The study was funded by the National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. The investigators and Dr. Cavalieri declared no competing interests. Dr. Licitra disclosed relationships AstraZeneca, Bristol Myers Squibb, and Hoffmann-La Roche.

[email protected]

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

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

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

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

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

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

Dermatologists cautioned colleagues to be aware of special hazards facing the LGBTQ community: A higher risk of skin cancer among gay men, possibly because of excess ultraviolet exposure, and acne in transgender people, who are especially vulnerable to acne because of hormone therapy.

The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”

Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).

When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P  = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).

Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.

For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”

Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.

In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.

Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.

Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.

What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.

Hormone therapy and acne

In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.

“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.

The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.

In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.

Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).

Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.

Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”

Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.

“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”

Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.

Dermatologists cautioned colleagues to be aware of special hazards facing the LGBTQ community: A higher risk of skin cancer among gay men, possibly because of excess ultraviolet exposure, and acne in transgender people, who are especially vulnerable to acne because of hormone therapy.

The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”

Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).

When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P  = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).

Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.

For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”

Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.

In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.

Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.

Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.

What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.

Hormone therapy and acne

In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.

“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.

The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.

In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.

Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).

Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.

Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”

Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.

“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”

Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.

Dermatologists cautioned colleagues to be aware of special hazards facing the LGBTQ community: A higher risk of skin cancer among gay men, possibly because of excess ultraviolet exposure, and acne in transgender people, who are especially vulnerable to acne because of hormone therapy.

The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”

Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).

When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P  = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).

Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.

For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”

Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.

In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.

Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.

Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.

What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.

Hormone therapy and acne

In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.

“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.

The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.

In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.

Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).

Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.

Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”

Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.

“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”

Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.

Cordis, part of Cardinal Health, has recalled certain lots of its Precise PRO Rx carotid stent system because of a risk of separation of the distal tip of the sheathed delivery system during use.

The Food and Drug Administration has classified this recall as class I, the most serious type, because of the potential for serious injury or death.

“If the device separates during use this may cause serious adverse events such as removal of the separated tip from the carotid artery, embolization distally, or stroke,” noted the recall notice posted on the FDA website.

To date, there have been seven complaints, including five reported injuries, related to this device issue. No deaths have been reported.

The Precise PRO Rx stent system is used in patients with stenotic lesions of the carotid arteries. The system includes a metal (nitinol) self-expanding stent preloaded on a delivery catheter used to place the stent.

The recall covers 7,300 devices made between October 2019 and August 2020 and distributed between Dec. 6, 2019, to Feb. 8, 2021.

The FDA has a complete list of product and lot numbers for the recalled devices on their website.

The company sent an urgent medical device recall letter to all affected customers asking them to check inventories and providing instructions on how to return any recalled product they have on hand.

Health care providers with questions about this recall can contact the company by email at [email protected] or by phone at 786-313-2087.

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

Cordis, part of Cardinal Health, has recalled certain lots of its Precise PRO Rx carotid stent system because of a risk of separation of the distal tip of the sheathed delivery system during use.

The Food and Drug Administration has classified this recall as class I, the most serious type, because of the potential for serious injury or death.

“If the device separates during use this may cause serious adverse events such as removal of the separated tip from the carotid artery, embolization distally, or stroke,” noted the recall notice posted on the FDA website.

To date, there have been seven complaints, including five reported injuries, related to this device issue. No deaths have been reported.

The Precise PRO Rx stent system is used in patients with stenotic lesions of the carotid arteries. The system includes a metal (nitinol) self-expanding stent preloaded on a delivery catheter used to place the stent.

The recall covers 7,300 devices made between October 2019 and August 2020 and distributed between Dec. 6, 2019, to Feb. 8, 2021.

The FDA has a complete list of product and lot numbers for the recalled devices on their website.

The company sent an urgent medical device recall letter to all affected customers asking them to check inventories and providing instructions on how to return any recalled product they have on hand.

Health care providers with questions about this recall can contact the company by email at [email protected] or by phone at 786-313-2087.

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

Cordis, part of Cardinal Health, has recalled certain lots of its Precise PRO Rx carotid stent system because of a risk of separation of the distal tip of the sheathed delivery system during use.

The Food and Drug Administration has classified this recall as class I, the most serious type, because of the potential for serious injury or death.

“If the device separates during use this may cause serious adverse events such as removal of the separated tip from the carotid artery, embolization distally, or stroke,” noted the recall notice posted on the FDA website.

To date, there have been seven complaints, including five reported injuries, related to this device issue. No deaths have been reported.

The Precise PRO Rx stent system is used in patients with stenotic lesions of the carotid arteries. The system includes a metal (nitinol) self-expanding stent preloaded on a delivery catheter used to place the stent.

The recall covers 7,300 devices made between October 2019 and August 2020 and distributed between Dec. 6, 2019, to Feb. 8, 2021.

The FDA has a complete list of product and lot numbers for the recalled devices on their website.

The company sent an urgent medical device recall letter to all affected customers asking them to check inventories and providing instructions on how to return any recalled product they have on hand.

Health care providers with questions about this recall can contact the company by email at [email protected] or by phone at 786-313-2087.

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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