Roxanne Nelson Rn, BSN

SEATTLE – At least for now, the number of physicians trained to perform Mohs surgery is not only stable but appears to be increasing. New findings show that the number of new fellows offsets the attrition rate and that has been the case for the past 5 years.

Using CMS billing codes as a surrogate, the researchers found that there was a steady increase in the number of physicians who billed from 2015 to 2020. With the exception of 2020, which was the height of the COVID-19 pandemic, the number of times that a specific code was billed for increased on average by 4.7% annually.

“Thus, if the attrition rate remains stable, even with changes in board certification and potential payer eligibility restrictions, the number of physicians will continue to increase,” study author Ji Won Ahn, MD, who specializes in dermatology and Mohs surgery at University of Pittsburgh Medical Center, said at the annual meeting of the American College of Mohs Surgery, where she presented the results.

The growth in the number of Mohs surgeons has been fueled by several factors, including a rising incidence of skin cancer as well as the superior cure rates and cosmetic outcomes with the procedure. Reimbursement has been favorable and training pathways have expanded. A 2019 retrospective study reported that there were 2,240 dermatologists who performed Mohs surgery in the United States, with nearly all of them (94.6%) residing in metropolitan areas.

Dr. Ahn explained that it was important to define the workforce because of several new factors that will be affecting it in the future. “With the establishment of Micrographic Surgery and Dermatologic Oncology [MSDO] board certification that went into effect 2 years ago, potential future payer eligibility restrictions may be coming,” she said. “The adequacy of the Mohs surgery workforce is an important consideration.”

Another issue is that new board certification will be limited to fellowship-trained physicians after the first 5 years. “We wanted to compare these numbers with the fellowship numbers,” she said. “Although fellowship numbers are something that the college potentially has the power to change.”

Dr. Ahn and colleagues used the Centers for Medicare & Medicaid Services database to evaluate the use of the Current Procedural Terminology (CPT) code 17311, which is one of the most common billing codes for Mohs micrographic technique. Looking at data from 2015-2020, they found that there was an annual increase in the number of unique national provider identifiers (NPIs) billing for 17311, at an average rate of 75.6 per year.

The total number of times that 17311 was billed also increased from 2015 to 2019 at an average rate of 4.7% per year but declined in 2020 by 8.4%. “Overall, there was an average of 135 new NPIs that appeared and an average of 59.4 NPIs that stopped billing for 17311,” thus, an attrition rate of 59 surgeons, Dr. Ahn explained.

She emphasized that notably, the number of approved MSDO fellowship spots has remained stable since 2016 and is about 92 to 93 per year. “There are about 135 new surgeons and about two-thirds are new fellowship graduates,” she said.

The researchers were also interested in seeing how saturated each surgeon was and looked at the approximate number of cases that they were handling.

Of the physicians who billed 17311 through CMS, over 26% billed less than 100 times and more than 45% billed less than 200 times, and over 80% billed less than 500 times.

“One might be able to conclude that there might be some potential flexibility depending on the future need for surgeons,” she said.

The study was limited by several factors, one being that the researchers looked only at CPT code 17311 and not other designated codes for Mohs surgery. Other factors such as staff and space limitations were not accounted for since only billing data were used.

Dr. Ahn and her team are going to continue their work, and the next steps are to look at geographic trends and monitor for insurance network eligibility changes. “We are currently doing a workforce survey so we can better understand our current workforce rather than just historical data,” she concluded.

Asked to comment on the results, Vishal Patel, MD, assistant professor of dermatology and director of the cutaneous oncology program at George Washington University, Washington, who was not involved with the study, noted that the increase in the “billing rates of the first stage of Mohs micrographic surgery highlights not only the growing skin cancer epidemic, but also the number of providers who are providing these services. This underscores the importance of standardized training guidelines and board certifications of Mohs micrographic surgeons to assure high levels of patient care and the appropriate use of Mohs micrographic surgery,” he said.

No external funding of the study was reported. Dr. Ahn reported no relevant financial relationships. Dr. Patel is a consultant for Sanofi, Regeneron, and Almirall.
 

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

SEATTLE – At least for now, the number of physicians trained to perform Mohs surgery is not only stable but appears to be increasing. New findings show that the number of new fellows offsets the attrition rate and that has been the case for the past 5 years.

Using CMS billing codes as a surrogate, the researchers found that there was a steady increase in the number of physicians who billed from 2015 to 2020. With the exception of 2020, which was the height of the COVID-19 pandemic, the number of times that a specific code was billed for increased on average by 4.7% annually.

“Thus, if the attrition rate remains stable, even with changes in board certification and potential payer eligibility restrictions, the number of physicians will continue to increase,” study author Ji Won Ahn, MD, who specializes in dermatology and Mohs surgery at University of Pittsburgh Medical Center, said at the annual meeting of the American College of Mohs Surgery, where she presented the results.

The growth in the number of Mohs surgeons has been fueled by several factors, including a rising incidence of skin cancer as well as the superior cure rates and cosmetic outcomes with the procedure. Reimbursement has been favorable and training pathways have expanded. A 2019 retrospective study reported that there were 2,240 dermatologists who performed Mohs surgery in the United States, with nearly all of them (94.6%) residing in metropolitan areas.

Dr. Ahn explained that it was important to define the workforce because of several new factors that will be affecting it in the future. “With the establishment of Micrographic Surgery and Dermatologic Oncology [MSDO] board certification that went into effect 2 years ago, potential future payer eligibility restrictions may be coming,” she said. “The adequacy of the Mohs surgery workforce is an important consideration.”

Another issue is that new board certification will be limited to fellowship-trained physicians after the first 5 years. “We wanted to compare these numbers with the fellowship numbers,” she said. “Although fellowship numbers are something that the college potentially has the power to change.”

Dr. Ahn and colleagues used the Centers for Medicare & Medicaid Services database to evaluate the use of the Current Procedural Terminology (CPT) code 17311, which is one of the most common billing codes for Mohs micrographic technique. Looking at data from 2015-2020, they found that there was an annual increase in the number of unique national provider identifiers (NPIs) billing for 17311, at an average rate of 75.6 per year.

The total number of times that 17311 was billed also increased from 2015 to 2019 at an average rate of 4.7% per year but declined in 2020 by 8.4%. “Overall, there was an average of 135 new NPIs that appeared and an average of 59.4 NPIs that stopped billing for 17311,” thus, an attrition rate of 59 surgeons, Dr. Ahn explained.

She emphasized that notably, the number of approved MSDO fellowship spots has remained stable since 2016 and is about 92 to 93 per year. “There are about 135 new surgeons and about two-thirds are new fellowship graduates,” she said.

The researchers were also interested in seeing how saturated each surgeon was and looked at the approximate number of cases that they were handling.

Of the physicians who billed 17311 through CMS, over 26% billed less than 100 times and more than 45% billed less than 200 times, and over 80% billed less than 500 times.

“One might be able to conclude that there might be some potential flexibility depending on the future need for surgeons,” she said.

The study was limited by several factors, one being that the researchers looked only at CPT code 17311 and not other designated codes for Mohs surgery. Other factors such as staff and space limitations were not accounted for since only billing data were used.

Dr. Ahn and her team are going to continue their work, and the next steps are to look at geographic trends and monitor for insurance network eligibility changes. “We are currently doing a workforce survey so we can better understand our current workforce rather than just historical data,” she concluded.

Asked to comment on the results, Vishal Patel, MD, assistant professor of dermatology and director of the cutaneous oncology program at George Washington University, Washington, who was not involved with the study, noted that the increase in the “billing rates of the first stage of Mohs micrographic surgery highlights not only the growing skin cancer epidemic, but also the number of providers who are providing these services. This underscores the importance of standardized training guidelines and board certifications of Mohs micrographic surgeons to assure high levels of patient care and the appropriate use of Mohs micrographic surgery,” he said.

No external funding of the study was reported. Dr. Ahn reported no relevant financial relationships. Dr. Patel is a consultant for Sanofi, Regeneron, and Almirall.
 

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

SEATTLE – At least for now, the number of physicians trained to perform Mohs surgery is not only stable but appears to be increasing. New findings show that the number of new fellows offsets the attrition rate and that has been the case for the past 5 years.

Using CMS billing codes as a surrogate, the researchers found that there was a steady increase in the number of physicians who billed from 2015 to 2020. With the exception of 2020, which was the height of the COVID-19 pandemic, the number of times that a specific code was billed for increased on average by 4.7% annually.

“Thus, if the attrition rate remains stable, even with changes in board certification and potential payer eligibility restrictions, the number of physicians will continue to increase,” study author Ji Won Ahn, MD, who specializes in dermatology and Mohs surgery at University of Pittsburgh Medical Center, said at the annual meeting of the American College of Mohs Surgery, where she presented the results.

The growth in the number of Mohs surgeons has been fueled by several factors, including a rising incidence of skin cancer as well as the superior cure rates and cosmetic outcomes with the procedure. Reimbursement has been favorable and training pathways have expanded. A 2019 retrospective study reported that there were 2,240 dermatologists who performed Mohs surgery in the United States, with nearly all of them (94.6%) residing in metropolitan areas.

Dr. Ahn explained that it was important to define the workforce because of several new factors that will be affecting it in the future. “With the establishment of Micrographic Surgery and Dermatologic Oncology [MSDO] board certification that went into effect 2 years ago, potential future payer eligibility restrictions may be coming,” she said. “The adequacy of the Mohs surgery workforce is an important consideration.”

Another issue is that new board certification will be limited to fellowship-trained physicians after the first 5 years. “We wanted to compare these numbers with the fellowship numbers,” she said. “Although fellowship numbers are something that the college potentially has the power to change.”

Dr. Ahn and colleagues used the Centers for Medicare & Medicaid Services database to evaluate the use of the Current Procedural Terminology (CPT) code 17311, which is one of the most common billing codes for Mohs micrographic technique. Looking at data from 2015-2020, they found that there was an annual increase in the number of unique national provider identifiers (NPIs) billing for 17311, at an average rate of 75.6 per year.

The total number of times that 17311 was billed also increased from 2015 to 2019 at an average rate of 4.7% per year but declined in 2020 by 8.4%. “Overall, there was an average of 135 new NPIs that appeared and an average of 59.4 NPIs that stopped billing for 17311,” thus, an attrition rate of 59 surgeons, Dr. Ahn explained.

She emphasized that notably, the number of approved MSDO fellowship spots has remained stable since 2016 and is about 92 to 93 per year. “There are about 135 new surgeons and about two-thirds are new fellowship graduates,” she said.

The researchers were also interested in seeing how saturated each surgeon was and looked at the approximate number of cases that they were handling.

Of the physicians who billed 17311 through CMS, over 26% billed less than 100 times and more than 45% billed less than 200 times, and over 80% billed less than 500 times.

“One might be able to conclude that there might be some potential flexibility depending on the future need for surgeons,” she said.

The study was limited by several factors, one being that the researchers looked only at CPT code 17311 and not other designated codes for Mohs surgery. Other factors such as staff and space limitations were not accounted for since only billing data were used.

Dr. Ahn and her team are going to continue their work, and the next steps are to look at geographic trends and monitor for insurance network eligibility changes. “We are currently doing a workforce survey so we can better understand our current workforce rather than just historical data,” she concluded.

Asked to comment on the results, Vishal Patel, MD, assistant professor of dermatology and director of the cutaneous oncology program at George Washington University, Washington, who was not involved with the study, noted that the increase in the “billing rates of the first stage of Mohs micrographic surgery highlights not only the growing skin cancer epidemic, but also the number of providers who are providing these services. This underscores the importance of standardized training guidelines and board certifications of Mohs micrographic surgeons to assure high levels of patient care and the appropriate use of Mohs micrographic surgery,” he said.

No external funding of the study was reported. Dr. Ahn reported no relevant financial relationships. Dr. Patel is a consultant for Sanofi, Regeneron, and Almirall.
 

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

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

A New Mexico oncologist has once again found himself at odds with the law.    

Mohamed Aswad, MD, was still under probation for a past misdemeanor involving misbranded cancer drugs when he allegedly underdosed chemotherapy in a patient with colon cancer. The patient later died.

In a wrongful death case, a jury has awarded $2.3 million in damages to the patient’s wife. The patient, James Hoag, was diagnosed with stage IIIB colon cancer in 2015. He underwent surgery and then went for chemotherapy to Dr. Aswad, who was the only oncologist in the area.

Mr. Hoag’s attorneys alleged that Dr. Aswad “recklessly administered” abnormally low doses of chemotherapy, and dragged out the normal 6-month regimen to 14 months, in an attempt to “unduly profit.”

“It was statistically likely that James would beat his cancer with proper treatment,” said his lawyers during the trial, according to a report in the Albuquerque Journal.

The jury deliberated for only 4 hours, and found that negligence by Dr. Aswad was a proximate cause of the patient’s “lost chance to avoid the loss of his life and resulting damages,” and the jury further described Dr. Aswad’s actions as “wanton,” according to a verdict form filed in the case.

The form also shows that the jury decided Dr. Aswad had obtained Mr. Hoag’s informed consent as to the treatment, but still felt that negligence was a cause of Mr. Hoag’s injury and damages. The original judgment of $2.9 million in damages was subsequently reduced to $2.3 million as the jury found Mr. Hoag was 30% responsible for his injuries.

Dr. Aswad could not be reached for comment. The Albuquerque Journal reports that he plans to appeal the verdict.
 

Only oncologist in the county

The patient had lived in the rural community of Deming, N.M. following his retirement from a career in law enforcement in Michigan. He was diagnosed with colon cancer in 2015, underwent surgical resection, and then went to Dr. Aswad for follow-up chemotherapy.

Dr. Aswad was the only oncologist in the area. Like many other rural communities throughout the United States, this region has a severe shortage of medical specialists.

Sheila Hoag, the patient’s widow, testified during the trial that following her husband’s surgery in August 2015, which removed the tumor, his “prognosis was very good because they had caught it before it spread.” He had an estimated 5-year survival of about 69%.

However, even though Dr. Aswad followed the National Comprehensive Cancer Network (NCCN) guidelines for adjuvant chemotherapy, he did not use the proper dosing. According to trial testimony, he administered “woefully lower doses” than are recommended, and also exceeded the recommended 6-month duration of chemotherapy by more than double. In addition, Dr. Aswad also failed to adequately monitor the disease during treatment, said Hoag’s lawyers.

Aswad has denied the charges and says that he prescribed a modified regimen spread out over a longer period of time because his patient had requested it. He said that Mr. Hoag did not want to undergo chemotherapy that could cause significant side effects, and this was the reason for the altered treatment plan.

However, the chemotherapy failed to slow the cancer’s progression, and Mr. Hoag never returned to see him after November 2016.

By December 2017, Mr. Hoag had been hospitalized and was being treated by another oncologist, located in Las Cruces, 62 miles away from his home. The new oncologist administered the standard treatment, but by then his cancer had metastasized. Mr. Hoag died in 2020 at age 59.
 

Previous misdemeanor with misbranded drugs

At the time he was treating Mr. Hoag, Dr. Aswad was on federal probation after pleading guilty in 2014 to one misdemeanor count of the unlawful introduction of misbranded drugs into interstate commerce.

Dr. Aswad had treated cancer patients with a “misbranded” drug imported from abroad and not approved by the U.S. Food and Drug Administration (FDA). Altuzan is a form of bevacizumab that is approved for use in Turkey but not the United States. Between July 2010 and April 2012, Dr. Aswad ordered prescription cancer drugs, including Altuzan, from a Canadian company and then administered the “misbranded” drugs to his patients.

A prescription drug is considered to be “misbranded” if it is manufactured in a facility that has not been registered with the FDA for commercial distribution within the United States.

According to various media reports, Dr. Aswad paid significantly less for these drugs than he would have if had he purchased the U.S.-approved product bearing the same brand or generic name, and then billed federal programs such as Medicare for the full price. He has admitted to making just under $1.3 million in profits.

Under the terms of the plea agreement, he was sentenced to three years of probation, required to pay just under $1.3 million in restitution to Medicare and Tricare, the victims of his criminal conduct, and also to forfeit $750,000, which represented part of his net criminal proceeds, to the United States.

At the trial, Dr. Aswad denied that there was any profit motive in extending Mr. Hoag’s treatment, and in a 2019 deposition, he also denied he was under financial pressure to increase his billings because of the $2 million debt that he owed because of the misbranded drugs fine.
 

Allowed to resume practice

In late 2015, Dr. Aswad was essentially barred by the federal government from accepting any reimbursement from Medicaid or Medicare for a minimum of 13 years. But because of the urgent need for medical specialists, the New Mexico Human Services Department requested a waiver that would permit him to continuing treating cancer patients since he is the only oncologist in Luna County.

He is currently allowed to treat Medicaid and Medicare patients in four other medically underserved New Mexico counties.

Dr. Aswad, a graduate of the University of Aleppo, in Syria, had an internal medicine residency at Our Lady of Mercy Hospital in New York City, where he also had a fellowship in oncology and hematology. He then settled in Deming and has been licensed in New Mexico since 2003.

With the onset of the COVID-19 pandemic, which caused major disruption to healthcare services, Medicare & Medicaid Services officials requested that Dr. Aswad also be allowed to provide internal medicine services for Medicare patients in Catron and Hildalgo counties for the “duration of the Coronavirus Disease 2019 public health emergency declared by the federal government in January 2020.”

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

In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.

Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.

At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.

In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.

The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.

“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.

The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO₂ concentration, or needed an intravenous infusion of vasopressors.

In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.

Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.

At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.

A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).

In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.

At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.

Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.

“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.

Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).

“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.

Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.

In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.

Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.

At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.

In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.

The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.

“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.

The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO₂ concentration, or needed an intravenous infusion of vasopressors.

In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.

Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.

At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.

A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).

In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.

At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.

Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.

“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.

Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).

“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.

Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.

In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.

Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.

At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.

In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.

The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.

“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.

The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO₂ concentration, or needed an intravenous infusion of vasopressors.

In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.

Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.

At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.

A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).

In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.

At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.

Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.

“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.

Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).

“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.

Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.

Carboplatin plus paclitaxel should now be considered the standard of care for patients with advanced anal cancer, in place of the standard combination of 5-fluorouracil (5-FU) and cisplatin, say experts discussing results from InterAAct, the first international prospective randomized trial in advanced anal cancer.

In the head-to-head trial, both combinations achieved a similar overall response rate — 59% for carboplatin plus paclitaxel and 57% for 5-FU plus cisplatin.

However, the 5-FU/cisplatin regimen was associated with significantly more adverse events, and there was a trend toward longer survival with carboplatin plus paclitaxel.

Median overall survival was 12.3 months for cisplatin plus 5-FU vs 20 months for carboplatin plus paclitaxel (adjusted hazard ratio [HR], 1.78; P =.059).

Serious adverse events were reported by more patients on cisplatin plus 5-FU vs carboplatin plus paclitaxel (62% vs. 36%; P =.016). The two regimens had different toxicity profiles, with more neutropenia and anemia observed in the carboplatin plus paclitaxel group, but more nausea, vomiting, mucositis, and diarrhea with cisplatin plus 5-FU.

“I think many of us were not surprised that the response rate was equivalent for the two arms but are pleasantly surprised by the difference in toxicity and the impact on survival,” said coauthor Cathy Eng, MD, chair in surgical and medical oncology at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

“We feel fairly confident that the carbo/taxol arm is the new arm to build upon,” she added.

“I think in comparison to the standard 5-FU/cisplatin, which was the control arm of the trial, this regimen should be considered the new standard of care,” said Eng.

Eng told Medscape Medical News that she doesn’t think that it needs further validation. “This is considered a rare cancer in the US,” she said. “The primary endpoint was feasibility of this international effort, which we established. If the response rate was equivalent, the less toxic regimen would be considered.”

“We fulfilled our primary endpoint of wanting to identify the best chemotherapy backbone to build upon,” she added.

These findings were initially presented at the European Society of Medical Oncology 2018 annual meeting, and reported by Medscape Medical News at the time. The full results were published earlier this month in the Journal of Clinical Oncology.

“The InterAAct trial has established carboplatin-paclitaxel as a new standard of care in this population in the frontline setting,” commented Sarbajit Mukherjee, MD, assistant professor of oncology at Roswell Park Comprehensive Cancer, Buffalo, New York, who was approached for an independent comment. “Clinicians should start using this regimen now, and it is also supported by the National Comprehensive Cancer Network guidelines.”

He emphasized the need for caution in interpreting the survival data because overall survival was not the primary endpoint of the study. “However, I do think that we should use this chemo regimen as a backbone for future randomized studies in this rare disease population,” said Mukherjee, who was not involved with the study.
 

Study Details

Anal cancer is rare, accounting for less than 3% of all gastrointestinal malignancies, but there has been a “dramatic” rise in incidence in recent decades, as previously reported by Medscape Medical News.  

Most patients present with localized or locally advanced disease and are treated with chemoradiotherapy with curative intent, the authors explain. However, metastatic dissemination occurs in about 10% of these patients, whereas <10% of all anal cancer patients present with metastatic disease de novo.

For patients with metastatic disease and for those with inoperable disease, the prognosis is poor, with relative 5-year survival rates of about 30%. Palliative chemotherapy is routinely offered, but to date, there have been no randomized controlled trials to inform clinicians of the optimal chemotherapy regimen in this setting.

International guidelines have suggested a platinum agent combined with fluoropyrimidine for the first-line treatment of advanced anal cancer, but this recommendation is based on limited evidence from single-arm phase 2 studies. The International Rare Cancers Initiative Anal Cancer Working Group recognized the evidence gap in clinical decision-making for patients with advanced cancer as an area of unmet clinical need, prompting the global InterAAct trial.

The trial involved 91 patients with locally recurrent inoperable or metastatic squamous cell carcinoma of the anus from 60 sites in North America, Europe and Australia. They were randomly assigned to receive either cisplatin 60 mg/m² (day 1) plus 5-FU 1000 mg/m² (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m² (days 1, 8, and 15) every 28 days. Patients were treated for 24 weeks or until disease progression, intolerable toxicity, or withdrawal of consent.

A “pick the winner” study design was used, in which the least toxic regimen would be selected as the “winner” if no significant difference in objective response rate between treatment groups was detected.

At a median follow-up of 28.6 months, the overall response rate did not differ significantly between both groups. The complete response rate was 17% with 5-FU/cisplatin and 12.8% with carboplatin-paclitaxel. Disease progression occurred in 22.9% of patients in the 5-FU/cisplatin group and 15.4% in the carboplatin-paclitaxel group.

The median progression-free survival was 5.7 months for cisplatin plus 5-FU compared with 8.1 months for carboplatin plus paclitaxel. The difference was not statistically significant. After adjusting for confounders, the HR was 1.17 (P = .564).

As already noted, there was a trend toward a significant difference in overall survival of almost 8 months favoring the carboplatin plus paclitaxel regimen. In addition, there was a significant difference in toxicity between the two regimens. 

Commenting on the study, Michael Buckstein, MD, PhD, assistant professor, Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York City, noted that even though “this study technically did not meet its endpoint of improved objective response rate and there was only a trend toward improved overall survival, the results presented here, especially with regard to toxicity, are very encouraging for a rare disease in a challenging population.”

Buckstein, who was not associated with the current research, added: “The trial is small, had problems in accrual, very few HIV patients, and was technically negative, so it’s hard to say this should be a ‘standard of care’ but it certainly should be considered ‘standard of practice’ and strongly considered for first-line therapy.”

The next US trial to follow InterAAct will look at the addition of immunotherapy to carboplatin/paclitaxel. This is the phase 3 EA2176 trial of carboplatin/paclitaxel ± nivolumab (plus maintenance), and it will have a primary endpoint of progression-free survival. “It will likely be open this summer, if not early fall, and will enroll 208 patients,” Eng commented.

The current study was supported by Cancer Research UK, AGITG, and ECOG-ACRIN. Eng has disclosed relationships with Bayer Schering Pharma, Foundation of Medicine, Array BioPharma, and Natera. Mukherjee and Buckstein have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Carboplatin plus paclitaxel should now be considered the standard of care for patients with advanced anal cancer, in place of the standard combination of 5-fluorouracil (5-FU) and cisplatin, say experts discussing results from InterAAct, the first international prospective randomized trial in advanced anal cancer.

In the head-to-head trial, both combinations achieved a similar overall response rate — 59% for carboplatin plus paclitaxel and 57% for 5-FU plus cisplatin.

However, the 5-FU/cisplatin regimen was associated with significantly more adverse events, and there was a trend toward longer survival with carboplatin plus paclitaxel.

Median overall survival was 12.3 months for cisplatin plus 5-FU vs 20 months for carboplatin plus paclitaxel (adjusted hazard ratio [HR], 1.78; P =.059).

Serious adverse events were reported by more patients on cisplatin plus 5-FU vs carboplatin plus paclitaxel (62% vs. 36%; P =.016). The two regimens had different toxicity profiles, with more neutropenia and anemia observed in the carboplatin plus paclitaxel group, but more nausea, vomiting, mucositis, and diarrhea with cisplatin plus 5-FU.

“I think many of us were not surprised that the response rate was equivalent for the two arms but are pleasantly surprised by the difference in toxicity and the impact on survival,” said coauthor Cathy Eng, MD, chair in surgical and medical oncology at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

“We feel fairly confident that the carbo/taxol arm is the new arm to build upon,” she added.

“I think in comparison to the standard 5-FU/cisplatin, which was the control arm of the trial, this regimen should be considered the new standard of care,” said Eng.

Eng told Medscape Medical News that she doesn’t think that it needs further validation. “This is considered a rare cancer in the US,” she said. “The primary endpoint was feasibility of this international effort, which we established. If the response rate was equivalent, the less toxic regimen would be considered.”

“We fulfilled our primary endpoint of wanting to identify the best chemotherapy backbone to build upon,” she added.

These findings were initially presented at the European Society of Medical Oncology 2018 annual meeting, and reported by Medscape Medical News at the time. The full results were published earlier this month in the Journal of Clinical Oncology.

“The InterAAct trial has established carboplatin-paclitaxel as a new standard of care in this population in the frontline setting,” commented Sarbajit Mukherjee, MD, assistant professor of oncology at Roswell Park Comprehensive Cancer, Buffalo, New York, who was approached for an independent comment. “Clinicians should start using this regimen now, and it is also supported by the National Comprehensive Cancer Network guidelines.”

He emphasized the need for caution in interpreting the survival data because overall survival was not the primary endpoint of the study. “However, I do think that we should use this chemo regimen as a backbone for future randomized studies in this rare disease population,” said Mukherjee, who was not involved with the study.
 

Study Details

Anal cancer is rare, accounting for less than 3% of all gastrointestinal malignancies, but there has been a “dramatic” rise in incidence in recent decades, as previously reported by Medscape Medical News.  

Most patients present with localized or locally advanced disease and are treated with chemoradiotherapy with curative intent, the authors explain. However, metastatic dissemination occurs in about 10% of these patients, whereas <10% of all anal cancer patients present with metastatic disease de novo.

For patients with metastatic disease and for those with inoperable disease, the prognosis is poor, with relative 5-year survival rates of about 30%. Palliative chemotherapy is routinely offered, but to date, there have been no randomized controlled trials to inform clinicians of the optimal chemotherapy regimen in this setting.

International guidelines have suggested a platinum agent combined with fluoropyrimidine for the first-line treatment of advanced anal cancer, but this recommendation is based on limited evidence from single-arm phase 2 studies. The International Rare Cancers Initiative Anal Cancer Working Group recognized the evidence gap in clinical decision-making for patients with advanced cancer as an area of unmet clinical need, prompting the global InterAAct trial.

The trial involved 91 patients with locally recurrent inoperable or metastatic squamous cell carcinoma of the anus from 60 sites in North America, Europe and Australia. They were randomly assigned to receive either cisplatin 60 mg/m² (day 1) plus 5-FU 1000 mg/m² (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m² (days 1, 8, and 15) every 28 days. Patients were treated for 24 weeks or until disease progression, intolerable toxicity, or withdrawal of consent.

A “pick the winner” study design was used, in which the least toxic regimen would be selected as the “winner” if no significant difference in objective response rate between treatment groups was detected.

At a median follow-up of 28.6 months, the overall response rate did not differ significantly between both groups. The complete response rate was 17% with 5-FU/cisplatin and 12.8% with carboplatin-paclitaxel. Disease progression occurred in 22.9% of patients in the 5-FU/cisplatin group and 15.4% in the carboplatin-paclitaxel group.

The median progression-free survival was 5.7 months for cisplatin plus 5-FU compared with 8.1 months for carboplatin plus paclitaxel. The difference was not statistically significant. After adjusting for confounders, the HR was 1.17 (P = .564).

As already noted, there was a trend toward a significant difference in overall survival of almost 8 months favoring the carboplatin plus paclitaxel regimen. In addition, there was a significant difference in toxicity between the two regimens. 

Commenting on the study, Michael Buckstein, MD, PhD, assistant professor, Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York City, noted that even though “this study technically did not meet its endpoint of improved objective response rate and there was only a trend toward improved overall survival, the results presented here, especially with regard to toxicity, are very encouraging for a rare disease in a challenging population.”

Buckstein, who was not associated with the current research, added: “The trial is small, had problems in accrual, very few HIV patients, and was technically negative, so it’s hard to say this should be a ‘standard of care’ but it certainly should be considered ‘standard of practice’ and strongly considered for first-line therapy.”

The next US trial to follow InterAAct will look at the addition of immunotherapy to carboplatin/paclitaxel. This is the phase 3 EA2176 trial of carboplatin/paclitaxel ± nivolumab (plus maintenance), and it will have a primary endpoint of progression-free survival. “It will likely be open this summer, if not early fall, and will enroll 208 patients,” Eng commented.

The current study was supported by Cancer Research UK, AGITG, and ECOG-ACRIN. Eng has disclosed relationships with Bayer Schering Pharma, Foundation of Medicine, Array BioPharma, and Natera. Mukherjee and Buckstein have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Carboplatin plus paclitaxel should now be considered the standard of care for patients with advanced anal cancer, in place of the standard combination of 5-fluorouracil (5-FU) and cisplatin, say experts discussing results from InterAAct, the first international prospective randomized trial in advanced anal cancer.

In the head-to-head trial, both combinations achieved a similar overall response rate — 59% for carboplatin plus paclitaxel and 57% for 5-FU plus cisplatin.

However, the 5-FU/cisplatin regimen was associated with significantly more adverse events, and there was a trend toward longer survival with carboplatin plus paclitaxel.

Median overall survival was 12.3 months for cisplatin plus 5-FU vs 20 months for carboplatin plus paclitaxel (adjusted hazard ratio [HR], 1.78; P =.059).

Serious adverse events were reported by more patients on cisplatin plus 5-FU vs carboplatin plus paclitaxel (62% vs. 36%; P =.016). The two regimens had different toxicity profiles, with more neutropenia and anemia observed in the carboplatin plus paclitaxel group, but more nausea, vomiting, mucositis, and diarrhea with cisplatin plus 5-FU.

“I think many of us were not surprised that the response rate was equivalent for the two arms but are pleasantly surprised by the difference in toxicity and the impact on survival,” said coauthor Cathy Eng, MD, chair in surgical and medical oncology at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

“We feel fairly confident that the carbo/taxol arm is the new arm to build upon,” she added.

“I think in comparison to the standard 5-FU/cisplatin, which was the control arm of the trial, this regimen should be considered the new standard of care,” said Eng.

Eng told Medscape Medical News that she doesn’t think that it needs further validation. “This is considered a rare cancer in the US,” she said. “The primary endpoint was feasibility of this international effort, which we established. If the response rate was equivalent, the less toxic regimen would be considered.”

“We fulfilled our primary endpoint of wanting to identify the best chemotherapy backbone to build upon,” she added.

These findings were initially presented at the European Society of Medical Oncology 2018 annual meeting, and reported by Medscape Medical News at the time. The full results were published earlier this month in the Journal of Clinical Oncology.

“The InterAAct trial has established carboplatin-paclitaxel as a new standard of care in this population in the frontline setting,” commented Sarbajit Mukherjee, MD, assistant professor of oncology at Roswell Park Comprehensive Cancer, Buffalo, New York, who was approached for an independent comment. “Clinicians should start using this regimen now, and it is also supported by the National Comprehensive Cancer Network guidelines.”

He emphasized the need for caution in interpreting the survival data because overall survival was not the primary endpoint of the study. “However, I do think that we should use this chemo regimen as a backbone for future randomized studies in this rare disease population,” said Mukherjee, who was not involved with the study.
 

Study Details

Anal cancer is rare, accounting for less than 3% of all gastrointestinal malignancies, but there has been a “dramatic” rise in incidence in recent decades, as previously reported by Medscape Medical News.  

Most patients present with localized or locally advanced disease and are treated with chemoradiotherapy with curative intent, the authors explain. However, metastatic dissemination occurs in about 10% of these patients, whereas <10% of all anal cancer patients present with metastatic disease de novo.

For patients with metastatic disease and for those with inoperable disease, the prognosis is poor, with relative 5-year survival rates of about 30%. Palliative chemotherapy is routinely offered, but to date, there have been no randomized controlled trials to inform clinicians of the optimal chemotherapy regimen in this setting.

International guidelines have suggested a platinum agent combined with fluoropyrimidine for the first-line treatment of advanced anal cancer, but this recommendation is based on limited evidence from single-arm phase 2 studies. The International Rare Cancers Initiative Anal Cancer Working Group recognized the evidence gap in clinical decision-making for patients with advanced cancer as an area of unmet clinical need, prompting the global InterAAct trial.

The trial involved 91 patients with locally recurrent inoperable or metastatic squamous cell carcinoma of the anus from 60 sites in North America, Europe and Australia. They were randomly assigned to receive either cisplatin 60 mg/m² (day 1) plus 5-FU 1000 mg/m² (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m² (days 1, 8, and 15) every 28 days. Patients were treated for 24 weeks or until disease progression, intolerable toxicity, or withdrawal of consent.

A “pick the winner” study design was used, in which the least toxic regimen would be selected as the “winner” if no significant difference in objective response rate between treatment groups was detected.

At a median follow-up of 28.6 months, the overall response rate did not differ significantly between both groups. The complete response rate was 17% with 5-FU/cisplatin and 12.8% with carboplatin-paclitaxel. Disease progression occurred in 22.9% of patients in the 5-FU/cisplatin group and 15.4% in the carboplatin-paclitaxel group.

The median progression-free survival was 5.7 months for cisplatin plus 5-FU compared with 8.1 months for carboplatin plus paclitaxel. The difference was not statistically significant. After adjusting for confounders, the HR was 1.17 (P = .564).

As already noted, there was a trend toward a significant difference in overall survival of almost 8 months favoring the carboplatin plus paclitaxel regimen. In addition, there was a significant difference in toxicity between the two regimens. 

Commenting on the study, Michael Buckstein, MD, PhD, assistant professor, Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York City, noted that even though “this study technically did not meet its endpoint of improved objective response rate and there was only a trend toward improved overall survival, the results presented here, especially with regard to toxicity, are very encouraging for a rare disease in a challenging population.”

Buckstein, who was not associated with the current research, added: “The trial is small, had problems in accrual, very few HIV patients, and was technically negative, so it’s hard to say this should be a ‘standard of care’ but it certainly should be considered ‘standard of practice’ and strongly considered for first-line therapy.”

The next US trial to follow InterAAct will look at the addition of immunotherapy to carboplatin/paclitaxel. This is the phase 3 EA2176 trial of carboplatin/paclitaxel ± nivolumab (plus maintenance), and it will have a primary endpoint of progression-free survival. “It will likely be open this summer, if not early fall, and will enroll 208 patients,” Eng commented.

The current study was supported by Cancer Research UK, AGITG, and ECOG-ACRIN. Eng has disclosed relationships with Bayer Schering Pharma, Foundation of Medicine, Array BioPharma, and Natera. Mukherjee and Buckstein have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.