Gynecologic Cancer

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

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

A targeted genetic sequencing strategy effectively identified homologous recombination DNA repair deficiency in ovarian cancer patients, and may eventually help predict treatment response, a study suggests.

Previous research has identified homologous recombination DNA repair deficiency (HRD) as a biomarker for sensitivity to poly( ADP-ribose) polymerase inhibitors (PARPi) and platinum-based therapies in patients with ovarian and breast cancers, wrote Niklas Krumm, MD, of the University of Washington, Seattle, and colleagues.

Currently, direct genetic testing is the most widely used method to identify mutations in HRD-associated genes, but not all genes underlying HDD have been identified, therefore current HRD assays that don’t rely on gene-specific information have been considered more diagnostically useful, the researchers noted. Two genetic tests are approved by the Food and Drug Administration, which are the FoundationFocus CDX BRCA and myChoice CDx, the researchers wrote. The Foundation Focus CDX BRCA was approved in 2016, and myChoice CDx was approved in 2019.

“However, transparent, well-defined methods and criteria for diagnosing HRD by genomic scarring that are practical for smaller, academic, or private laboratories have not yet been established or widely implemented,” they said.

In the paper published in JCO Precision Oncology, the researchers said they developed a molecular testing strategy involving the use of common, polymorphic single-nucleotide polymorphisms (SNPs).

They used a panel of approximately 3,000 SNPs distributed across the genome to create a loss of heterozygosity (LOH) score that could identify HRD.

To determine the ability of LOH to diagnose HRD in ovarian cancers, the researchers examined 99 ovarian neoplasm–normal pairs using the LOH method, and compared results with patient mutational genotypes and HRD predictors. LOH scores of 11% or higher showed greater than 86% sensitivity for identifying tumors with HRD-causing mutations in an independent validation set, and a sensitivity of 90.9% across training and validation sets.

When LOH scores were compared to a validated genome-wide mutational signature assay (HRDetect) the sensitivity and specificity of an LOH score of 11% or higher were estimated at 96.7% and 50%, respectively, for determining HRD-positive tumors.

However, the researchers found poor concordance (statistically insignificant correlation) using their LOH capture design to diagnose HRD based on mutational signatures only from targeted regions. “We conclude that mutational signatures inferred from our diagnostic tumor panel are unable to accurately ascertain HRD status, likely because the absolute number of somatic variants that it is able to identify is insufficient,” they said.

LOH scores were not significantly correlated with treatment outcomes, which suggests that LOH score can be used to infer HRD status, rather than serving as a direct predictor of patient response to primary platinum therapy, the researchers said. The average LOH score was higher in patients whose cancers responded to platinum therapy than in those with no treatment response (17% vs. 15%) but this difference was not significant.


 

Study limitations

The research was limited by several factors, including the validation only for high-grade non–clear cell ovarian carcinomas, and LOH scores likely vary across cancer types, therefore more studies will be needed to optimize the strategy for different cancers, the researchers noted. Other potential limitations include the high level of tumor cellularity needed (30%), which will eliminate some specimens, they said.

Finally, the poor predictive value of LOH itself for treatment outcomes suggests a limitation of the HRD biomarker in this respect, the researchers concluded.
 

Potential advantages of using LOH method

However, the potential advantages of the LOH method include the minimal sequence reads and the ability to integrate the LOH into current targeted gene capture workflows, the researchers wrote, and the LOH score appears to be a reliable predictor of HRD positivity.

“Although we have found that the regions targeted by our assay are insufficient to identify HRD-associated mutational signatures, future refinements to this approach could integrate minimal additional sequencing targets designed to robustly identify such signatures in concert with LOH events,” they concluded.
 

Study shares the details of detection methodology

“Tumors with HRD are sensitive to certain cancer chemotherapeutic agents [PARP inhibitors],” said Dr. Krumm, in an interview. “Until recently, HR-deficient tumors were primarily identified via inactivating BRCA1 or BRCA2 mutations, but now it is understood that an entire repair pathway can be affected and can result in HRD. Therefore, we sought to implement an NGS-based approach that could detect the ‘HRD phenotype’ in the DNA of tumors,” he said.

The approach developed by Dr. Krumm and colleagues and presented in the current study “is not the first in the field, as some commercial tests have similar approaches,” he said. However, the current study is important, “because it openly publishes the methodology and detailed results of our validation work in bringing HRD detection online in our clinical lab,” he said.

“One of the advantages of a genome-wide approach is that we can identify HR-deficient tumors, even when BRCA1 and BRCA2 do not have any detectable loss-of-function mutations,” said Dr. Krumm. “HRD detection is a relatively young test in the field of next-generation sequencing (NGS)–based cancer diagnostics. One of the challenges currently is the lack of large, standardized reference data sets or reference materials that can be used to compare tests and methodology in a clinical setting. We hope that by publishing our methods, more data sets can be generated and published,” he said.

Some specific challenges to using the test clinically today include the need for a paired tumor plus blood sample, and the need for a relatively high fraction of tumor content in the sample, Dr. Krumm noted.

“This test is currently being used in a clinical setting at the University of Washington, as it is a laboratory-developed test (LDT) and part of our clinically validated NGS platform,” said Dr. Krumm. “This test highlights how LDTs can advance clinical testing capabilities and improve the care of our patients and illustrates the UW Medicine position that LDTs are a necessary and important part of the clinical care. That said, we anticipate that additional validation studies, including long-term clinical effectiveness and outcome studies, will be required to bring HRD testing into a commercial platform that undergoes FDA review,” he explained.

The study was supported by the Brotman Baty Institute for Precision Medicine, the National Institutes of Health, and the Department of Defense, Ovarian Cancer Research Program Clinical Development Award. Dr. Krumm disclosed stock and ownership interests in Reference Genomics.

A targeted genetic sequencing strategy effectively identified homologous recombination DNA repair deficiency in ovarian cancer patients, and may eventually help predict treatment response, a study suggests.

Previous research has identified homologous recombination DNA repair deficiency (HRD) as a biomarker for sensitivity to poly( ADP-ribose) polymerase inhibitors (PARPi) and platinum-based therapies in patients with ovarian and breast cancers, wrote Niklas Krumm, MD, of the University of Washington, Seattle, and colleagues.

Currently, direct genetic testing is the most widely used method to identify mutations in HRD-associated genes, but not all genes underlying HDD have been identified, therefore current HRD assays that don’t rely on gene-specific information have been considered more diagnostically useful, the researchers noted. Two genetic tests are approved by the Food and Drug Administration, which are the FoundationFocus CDX BRCA and myChoice CDx, the researchers wrote. The Foundation Focus CDX BRCA was approved in 2016, and myChoice CDx was approved in 2019.

“However, transparent, well-defined methods and criteria for diagnosing HRD by genomic scarring that are practical for smaller, academic, or private laboratories have not yet been established or widely implemented,” they said.

In the paper published in JCO Precision Oncology, the researchers said they developed a molecular testing strategy involving the use of common, polymorphic single-nucleotide polymorphisms (SNPs).

They used a panel of approximately 3,000 SNPs distributed across the genome to create a loss of heterozygosity (LOH) score that could identify HRD.

To determine the ability of LOH to diagnose HRD in ovarian cancers, the researchers examined 99 ovarian neoplasm–normal pairs using the LOH method, and compared results with patient mutational genotypes and HRD predictors. LOH scores of 11% or higher showed greater than 86% sensitivity for identifying tumors with HRD-causing mutations in an independent validation set, and a sensitivity of 90.9% across training and validation sets.

When LOH scores were compared to a validated genome-wide mutational signature assay (HRDetect) the sensitivity and specificity of an LOH score of 11% or higher were estimated at 96.7% and 50%, respectively, for determining HRD-positive tumors.

However, the researchers found poor concordance (statistically insignificant correlation) using their LOH capture design to diagnose HRD based on mutational signatures only from targeted regions. “We conclude that mutational signatures inferred from our diagnostic tumor panel are unable to accurately ascertain HRD status, likely because the absolute number of somatic variants that it is able to identify is insufficient,” they said.

LOH scores were not significantly correlated with treatment outcomes, which suggests that LOH score can be used to infer HRD status, rather than serving as a direct predictor of patient response to primary platinum therapy, the researchers said. The average LOH score was higher in patients whose cancers responded to platinum therapy than in those with no treatment response (17% vs. 15%) but this difference was not significant.


 

Study limitations

The research was limited by several factors, including the validation only for high-grade non–clear cell ovarian carcinomas, and LOH scores likely vary across cancer types, therefore more studies will be needed to optimize the strategy for different cancers, the researchers noted. Other potential limitations include the high level of tumor cellularity needed (30%), which will eliminate some specimens, they said.

Finally, the poor predictive value of LOH itself for treatment outcomes suggests a limitation of the HRD biomarker in this respect, the researchers concluded.
 

Potential advantages of using LOH method

However, the potential advantages of the LOH method include the minimal sequence reads and the ability to integrate the LOH into current targeted gene capture workflows, the researchers wrote, and the LOH score appears to be a reliable predictor of HRD positivity.

“Although we have found that the regions targeted by our assay are insufficient to identify HRD-associated mutational signatures, future refinements to this approach could integrate minimal additional sequencing targets designed to robustly identify such signatures in concert with LOH events,” they concluded.
 

Study shares the details of detection methodology

“Tumors with HRD are sensitive to certain cancer chemotherapeutic agents [PARP inhibitors],” said Dr. Krumm, in an interview. “Until recently, HR-deficient tumors were primarily identified via inactivating BRCA1 or BRCA2 mutations, but now it is understood that an entire repair pathway can be affected and can result in HRD. Therefore, we sought to implement an NGS-based approach that could detect the ‘HRD phenotype’ in the DNA of tumors,” he said.

The approach developed by Dr. Krumm and colleagues and presented in the current study “is not the first in the field, as some commercial tests have similar approaches,” he said. However, the current study is important, “because it openly publishes the methodology and detailed results of our validation work in bringing HRD detection online in our clinical lab,” he said.

“One of the advantages of a genome-wide approach is that we can identify HR-deficient tumors, even when BRCA1 and BRCA2 do not have any detectable loss-of-function mutations,” said Dr. Krumm. “HRD detection is a relatively young test in the field of next-generation sequencing (NGS)–based cancer diagnostics. One of the challenges currently is the lack of large, standardized reference data sets or reference materials that can be used to compare tests and methodology in a clinical setting. We hope that by publishing our methods, more data sets can be generated and published,” he said.

Some specific challenges to using the test clinically today include the need for a paired tumor plus blood sample, and the need for a relatively high fraction of tumor content in the sample, Dr. Krumm noted.

“This test is currently being used in a clinical setting at the University of Washington, as it is a laboratory-developed test (LDT) and part of our clinically validated NGS platform,” said Dr. Krumm. “This test highlights how LDTs can advance clinical testing capabilities and improve the care of our patients and illustrates the UW Medicine position that LDTs are a necessary and important part of the clinical care. That said, we anticipate that additional validation studies, including long-term clinical effectiveness and outcome studies, will be required to bring HRD testing into a commercial platform that undergoes FDA review,” he explained.

The study was supported by the Brotman Baty Institute for Precision Medicine, the National Institutes of Health, and the Department of Defense, Ovarian Cancer Research Program Clinical Development Award. Dr. Krumm disclosed stock and ownership interests in Reference Genomics.

A targeted genetic sequencing strategy effectively identified homologous recombination DNA repair deficiency in ovarian cancer patients, and may eventually help predict treatment response, a study suggests.

Previous research has identified homologous recombination DNA repair deficiency (HRD) as a biomarker for sensitivity to poly( ADP-ribose) polymerase inhibitors (PARPi) and platinum-based therapies in patients with ovarian and breast cancers, wrote Niklas Krumm, MD, of the University of Washington, Seattle, and colleagues.

Currently, direct genetic testing is the most widely used method to identify mutations in HRD-associated genes, but not all genes underlying HDD have been identified, therefore current HRD assays that don’t rely on gene-specific information have been considered more diagnostically useful, the researchers noted. Two genetic tests are approved by the Food and Drug Administration, which are the FoundationFocus CDX BRCA and myChoice CDx, the researchers wrote. The Foundation Focus CDX BRCA was approved in 2016, and myChoice CDx was approved in 2019.

“However, transparent, well-defined methods and criteria for diagnosing HRD by genomic scarring that are practical for smaller, academic, or private laboratories have not yet been established or widely implemented,” they said.

In the paper published in JCO Precision Oncology, the researchers said they developed a molecular testing strategy involving the use of common, polymorphic single-nucleotide polymorphisms (SNPs).

They used a panel of approximately 3,000 SNPs distributed across the genome to create a loss of heterozygosity (LOH) score that could identify HRD.

To determine the ability of LOH to diagnose HRD in ovarian cancers, the researchers examined 99 ovarian neoplasm–normal pairs using the LOH method, and compared results with patient mutational genotypes and HRD predictors. LOH scores of 11% or higher showed greater than 86% sensitivity for identifying tumors with HRD-causing mutations in an independent validation set, and a sensitivity of 90.9% across training and validation sets.

When LOH scores were compared to a validated genome-wide mutational signature assay (HRDetect) the sensitivity and specificity of an LOH score of 11% or higher were estimated at 96.7% and 50%, respectively, for determining HRD-positive tumors.

However, the researchers found poor concordance (statistically insignificant correlation) using their LOH capture design to diagnose HRD based on mutational signatures only from targeted regions. “We conclude that mutational signatures inferred from our diagnostic tumor panel are unable to accurately ascertain HRD status, likely because the absolute number of somatic variants that it is able to identify is insufficient,” they said.

LOH scores were not significantly correlated with treatment outcomes, which suggests that LOH score can be used to infer HRD status, rather than serving as a direct predictor of patient response to primary platinum therapy, the researchers said. The average LOH score was higher in patients whose cancers responded to platinum therapy than in those with no treatment response (17% vs. 15%) but this difference was not significant.


 

Study limitations

The research was limited by several factors, including the validation only for high-grade non–clear cell ovarian carcinomas, and LOH scores likely vary across cancer types, therefore more studies will be needed to optimize the strategy for different cancers, the researchers noted. Other potential limitations include the high level of tumor cellularity needed (30%), which will eliminate some specimens, they said.

Finally, the poor predictive value of LOH itself for treatment outcomes suggests a limitation of the HRD biomarker in this respect, the researchers concluded.
 

Potential advantages of using LOH method

However, the potential advantages of the LOH method include the minimal sequence reads and the ability to integrate the LOH into current targeted gene capture workflows, the researchers wrote, and the LOH score appears to be a reliable predictor of HRD positivity.

“Although we have found that the regions targeted by our assay are insufficient to identify HRD-associated mutational signatures, future refinements to this approach could integrate minimal additional sequencing targets designed to robustly identify such signatures in concert with LOH events,” they concluded.
 

Study shares the details of detection methodology

“Tumors with HRD are sensitive to certain cancer chemotherapeutic agents [PARP inhibitors],” said Dr. Krumm, in an interview. “Until recently, HR-deficient tumors were primarily identified via inactivating BRCA1 or BRCA2 mutations, but now it is understood that an entire repair pathway can be affected and can result in HRD. Therefore, we sought to implement an NGS-based approach that could detect the ‘HRD phenotype’ in the DNA of tumors,” he said.

The approach developed by Dr. Krumm and colleagues and presented in the current study “is not the first in the field, as some commercial tests have similar approaches,” he said. However, the current study is important, “because it openly publishes the methodology and detailed results of our validation work in bringing HRD detection online in our clinical lab,” he said.

“One of the advantages of a genome-wide approach is that we can identify HR-deficient tumors, even when BRCA1 and BRCA2 do not have any detectable loss-of-function mutations,” said Dr. Krumm. “HRD detection is a relatively young test in the field of next-generation sequencing (NGS)–based cancer diagnostics. One of the challenges currently is the lack of large, standardized reference data sets or reference materials that can be used to compare tests and methodology in a clinical setting. We hope that by publishing our methods, more data sets can be generated and published,” he said.

Some specific challenges to using the test clinically today include the need for a paired tumor plus blood sample, and the need for a relatively high fraction of tumor content in the sample, Dr. Krumm noted.

“This test is currently being used in a clinical setting at the University of Washington, as it is a laboratory-developed test (LDT) and part of our clinically validated NGS platform,” said Dr. Krumm. “This test highlights how LDTs can advance clinical testing capabilities and improve the care of our patients and illustrates the UW Medicine position that LDTs are a necessary and important part of the clinical care. That said, we anticipate that additional validation studies, including long-term clinical effectiveness and outcome studies, will be required to bring HRD testing into a commercial platform that undergoes FDA review,” he explained.

The study was supported by the Brotman Baty Institute for Precision Medicine, the National Institutes of Health, and the Department of Defense, Ovarian Cancer Research Program Clinical Development Award. Dr. Krumm disclosed stock and ownership interests in Reference Genomics.

CHICAGO – In the phase 3 MIRASOL study, the antibody-drug conjugate (ADC) mirvetuximab soravtansine-gynx (MIRV, Elahere, ImmunoGen) produced an overall survival benefit in women with platinum-resistant ovarian cancer.

The conclusion of this study marks the first time that a novel therapy has demonstrated an overall survival (OS) improvement in any phase 3 trial in this population, according to lead investigator Kathleen Moore, MD.

“We believe these data are practice changing and position mirvetuximab [soravtansine] as the new standard of care for patients with folate receptor–alpha positive, platinum-resistant ovarian cancer,” said Dr. Moore during a presentation of the study at a special session of the annual meeting of the American Society of Clinical Oncology devoted solely to the MIRASOL study.
 

New standard of care

Following Dr. Moore’s presentation, Roisin Eilish O’Cearbhaill, MD, served as a discussant, and she confirmed the trial’s importance.

“It has firmly established the role of mirvetuximab [soravtansine] in folate receptor–alpha high-expression, platinum-resistant ovarian cancer,” said Dr. O’Cearbhaill, who is Research director of the gynecologic medical oncology service and clinical director of the solid tumor, cellular therapy service at Memorial Sloan Kettering Cancer Center, New York.

Mirvetuximab soravtansine received accelerated FDA approval in November based on the results of the single-arm SORAYA trial, which demonstrated a progression-free survival (PFS) benefit in platinum-resistant patients who had been previously treated with one to three treatment regimens, at least one of which having included bevacizumab.

The new study compared MIRV with physician choice chemotherapy and found both a PFS and OS benefit in the MIRV arm. The results garnered significant enthusiasm from the audience, and others reacted positively as well.

“The results that she presented are just astounding, with a significant improvement in both progression-free and overall survival. I think certainly the overall survival needs to be highlighted here, because this is a patient population that’s notoriously difficult to treat,” said Ana Valente, MD, a gynecologic oncologist at the Ochsner Health System in New Orleans. Dr. Valente, who did not attend the presentation but was asked to comment on the study, is also a member of the Society of Gynecological Oncologist communications committee.

Unlike SORAYA, MIRASOL was open to patients who had not received bevacizumab, and Dr. Moore and colleagues found similar survival benefits in patients who had not received bevacizumab as in those who had, said Dr. Moore, who is the associate director of clinical research at Stephenson Cancer Center and director of the Oklahoma TSET Phase 1 Program, both in Oklahoma City. This opens the possibility of using MIRV instead of bevacizumab combined with chemotherapy in platinum-resistant patients.

“I think this data really shows you can move right to mirvetuximab [soravtansine] and feel pretty solid about the decision in a biomarker selected [population],” Dr. Moore said, during an interview.
 

Not just for high expression levels

MIRASOL was restricted to patients with high levels of expression of folate receptor–alpha, which is MIRV’s target on the surface of tumor cells. High expression is defined as at least 75% of viable tumor cells exhibiting a minimum of 2+ level membrane staining intensity by immunohistochemistry. That represents about 35% of patients, according to Dr. Moore, but she said that the drug also shows promise in patients with medium levels of folate receptor–alpha expression.

“I think it’s just going to be now starting to get those label extension studies launched to branch it out. Then you account for 60% of your population which [have] medium to high [expression levels], and that’s really where you see benefit,” said Dr. Moore. Medium expression levels of folate receptor–alpha are defined as 50% to greater than 75% of tumor cells with 2+ level membrane staining intensity.

She also noted that the FORWARD II trial combining mirvetuximab soravtansine with bevacizumab in platinum-resistant ovarian cancer is showing good results.

“We have really beautiful data [from FORWARD II]. If I have a medium expresser, I’m using the doublet [of MIRV and bevacizumab], and it works,” said Dr. Moore, while also pointing out that this remains an off-label use.

It’s possible that the drug could be extended even to low expression levels, defined as 25% to less than 50% of tumor cells with 2+ level membrane staining intensity. “[We are] currently working on that strategy with already available data,” said Dr. Moore.

She speculated that the improved OS may be attributed to the reduced toxicity of MIRV, compared with chemotherapy agents, which leaves patients feeling better and more able to pursue other treatments, which in turn may increase survival odds.

Dr. O’Cearbhaill touted the benefits of ADCs and their ability to target powerful cytotoxic agents while limiting side effects, and she is looking forward to more new therapies on the horizon.

“There are four [ADCs] in late stages of development [for platinum-resistant ovarian cancer], so hopefully there will be other ones coming online as well,” Dr. O’Cearbhaill said in an interview. “Then we’ll have to figure out how to sequence them, which drug will be best in class. Will we be just giving one or will be giving ADC followed by ADC?”
 

Study methods and results

The study enrolled 453 patients and randomized them to treatment with MIRV or investigator’s choice of chemotherapy, which could be paclitaxel, pegylated liposomal doxorubicin, or topotecan. The MIRV dose was 6 mg/kg adjusted ideal body weight every 3 weeks. The median age was 62 in the chemotherapy arm and 63 years in the MIRV arm. About 63% of the chemotherapy arm had prior bevacizumab exposure, as did 61% of the MIRV arm.

Median PFS was 5.62 months in the MIRV arm and 3.98 months in the chemotherapy arm (hazard ratio, 0.65; P less than .0001). The overall response rate was 42% in the MIRV arm and 16% in the chemotherapy arm (P < .0001).

The safety outcomes also favored MIRV: 42% experienced grade 3 or higher treatment-emergent adverse events (TEAEs) versus 54% in the chemotherapy group. Severe adverse events were also lower in MIRV, 24% versus 33%. Just 9% of patients in the MIRV discontinued because of TEAEs, compared with 16% in the chemotherapy arm.

MIRV was associated with blurred vision (41%), keratopathy (32%), and dry eye (28%), but these issues were generally manageable through collaboration with optometrists or ophthalmologists.

Dr. Moore and Dr. O’Cearbhaill reported receiving honoraria, research funding, and travel expenses from numerous pharmaceutical companies. Dr. O’Cearbhaill has consulted for or advised Aptitude Health, Bayer, Carina Biotech, Fresenius Kabi, GlaxoSmithKline, GOG Foundation, Immunogen, R-Pharm, Regeneron, and Seagen.

CHICAGO – In the phase 3 MIRASOL study, the antibody-drug conjugate (ADC) mirvetuximab soravtansine-gynx (MIRV, Elahere, ImmunoGen) produced an overall survival benefit in women with platinum-resistant ovarian cancer.

The conclusion of this study marks the first time that a novel therapy has demonstrated an overall survival (OS) improvement in any phase 3 trial in this population, according to lead investigator Kathleen Moore, MD.

“We believe these data are practice changing and position mirvetuximab [soravtansine] as the new standard of care for patients with folate receptor–alpha positive, platinum-resistant ovarian cancer,” said Dr. Moore during a presentation of the study at a special session of the annual meeting of the American Society of Clinical Oncology devoted solely to the MIRASOL study.
 

New standard of care

Following Dr. Moore’s presentation, Roisin Eilish O’Cearbhaill, MD, served as a discussant, and she confirmed the trial’s importance.

“It has firmly established the role of mirvetuximab [soravtansine] in folate receptor–alpha high-expression, platinum-resistant ovarian cancer,” said Dr. O’Cearbhaill, who is Research director of the gynecologic medical oncology service and clinical director of the solid tumor, cellular therapy service at Memorial Sloan Kettering Cancer Center, New York.

Mirvetuximab soravtansine received accelerated FDA approval in November based on the results of the single-arm SORAYA trial, which demonstrated a progression-free survival (PFS) benefit in platinum-resistant patients who had been previously treated with one to three treatment regimens, at least one of which having included bevacizumab.

The new study compared MIRV with physician choice chemotherapy and found both a PFS and OS benefit in the MIRV arm. The results garnered significant enthusiasm from the audience, and others reacted positively as well.

“The results that she presented are just astounding, with a significant improvement in both progression-free and overall survival. I think certainly the overall survival needs to be highlighted here, because this is a patient population that’s notoriously difficult to treat,” said Ana Valente, MD, a gynecologic oncologist at the Ochsner Health System in New Orleans. Dr. Valente, who did not attend the presentation but was asked to comment on the study, is also a member of the Society of Gynecological Oncologist communications committee.

Unlike SORAYA, MIRASOL was open to patients who had not received bevacizumab, and Dr. Moore and colleagues found similar survival benefits in patients who had not received bevacizumab as in those who had, said Dr. Moore, who is the associate director of clinical research at Stephenson Cancer Center and director of the Oklahoma TSET Phase 1 Program, both in Oklahoma City. This opens the possibility of using MIRV instead of bevacizumab combined with chemotherapy in platinum-resistant patients.

“I think this data really shows you can move right to mirvetuximab [soravtansine] and feel pretty solid about the decision in a biomarker selected [population],” Dr. Moore said, during an interview.
 

Not just for high expression levels

MIRASOL was restricted to patients with high levels of expression of folate receptor–alpha, which is MIRV’s target on the surface of tumor cells. High expression is defined as at least 75% of viable tumor cells exhibiting a minimum of 2+ level membrane staining intensity by immunohistochemistry. That represents about 35% of patients, according to Dr. Moore, but she said that the drug also shows promise in patients with medium levels of folate receptor–alpha expression.

“I think it’s just going to be now starting to get those label extension studies launched to branch it out. Then you account for 60% of your population which [have] medium to high [expression levels], and that’s really where you see benefit,” said Dr. Moore. Medium expression levels of folate receptor–alpha are defined as 50% to greater than 75% of tumor cells with 2+ level membrane staining intensity.

She also noted that the FORWARD II trial combining mirvetuximab soravtansine with bevacizumab in platinum-resistant ovarian cancer is showing good results.

“We have really beautiful data [from FORWARD II]. If I have a medium expresser, I’m using the doublet [of MIRV and bevacizumab], and it works,” said Dr. Moore, while also pointing out that this remains an off-label use.

It’s possible that the drug could be extended even to low expression levels, defined as 25% to less than 50% of tumor cells with 2+ level membrane staining intensity. “[We are] currently working on that strategy with already available data,” said Dr. Moore.

She speculated that the improved OS may be attributed to the reduced toxicity of MIRV, compared with chemotherapy agents, which leaves patients feeling better and more able to pursue other treatments, which in turn may increase survival odds.

Dr. O’Cearbhaill touted the benefits of ADCs and their ability to target powerful cytotoxic agents while limiting side effects, and she is looking forward to more new therapies on the horizon.

“There are four [ADCs] in late stages of development [for platinum-resistant ovarian cancer], so hopefully there will be other ones coming online as well,” Dr. O’Cearbhaill said in an interview. “Then we’ll have to figure out how to sequence them, which drug will be best in class. Will we be just giving one or will be giving ADC followed by ADC?”
 

Study methods and results

The study enrolled 453 patients and randomized them to treatment with MIRV or investigator’s choice of chemotherapy, which could be paclitaxel, pegylated liposomal doxorubicin, or topotecan. The MIRV dose was 6 mg/kg adjusted ideal body weight every 3 weeks. The median age was 62 in the chemotherapy arm and 63 years in the MIRV arm. About 63% of the chemotherapy arm had prior bevacizumab exposure, as did 61% of the MIRV arm.

Median PFS was 5.62 months in the MIRV arm and 3.98 months in the chemotherapy arm (hazard ratio, 0.65; P less than .0001). The overall response rate was 42% in the MIRV arm and 16% in the chemotherapy arm (P < .0001).

The safety outcomes also favored MIRV: 42% experienced grade 3 or higher treatment-emergent adverse events (TEAEs) versus 54% in the chemotherapy group. Severe adverse events were also lower in MIRV, 24% versus 33%. Just 9% of patients in the MIRV discontinued because of TEAEs, compared with 16% in the chemotherapy arm.

MIRV was associated with blurred vision (41%), keratopathy (32%), and dry eye (28%), but these issues were generally manageable through collaboration with optometrists or ophthalmologists.

Dr. Moore and Dr. O’Cearbhaill reported receiving honoraria, research funding, and travel expenses from numerous pharmaceutical companies. Dr. O’Cearbhaill has consulted for or advised Aptitude Health, Bayer, Carina Biotech, Fresenius Kabi, GlaxoSmithKline, GOG Foundation, Immunogen, R-Pharm, Regeneron, and Seagen.

CHICAGO – In the phase 3 MIRASOL study, the antibody-drug conjugate (ADC) mirvetuximab soravtansine-gynx (MIRV, Elahere, ImmunoGen) produced an overall survival benefit in women with platinum-resistant ovarian cancer.

The conclusion of this study marks the first time that a novel therapy has demonstrated an overall survival (OS) improvement in any phase 3 trial in this population, according to lead investigator Kathleen Moore, MD.

“We believe these data are practice changing and position mirvetuximab [soravtansine] as the new standard of care for patients with folate receptor–alpha positive, platinum-resistant ovarian cancer,” said Dr. Moore during a presentation of the study at a special session of the annual meeting of the American Society of Clinical Oncology devoted solely to the MIRASOL study.
 

New standard of care

Following Dr. Moore’s presentation, Roisin Eilish O’Cearbhaill, MD, served as a discussant, and she confirmed the trial’s importance.

“It has firmly established the role of mirvetuximab [soravtansine] in folate receptor–alpha high-expression, platinum-resistant ovarian cancer,” said Dr. O’Cearbhaill, who is Research director of the gynecologic medical oncology service and clinical director of the solid tumor, cellular therapy service at Memorial Sloan Kettering Cancer Center, New York.

Mirvetuximab soravtansine received accelerated FDA approval in November based on the results of the single-arm SORAYA trial, which demonstrated a progression-free survival (PFS) benefit in platinum-resistant patients who had been previously treated with one to three treatment regimens, at least one of which having included bevacizumab.

The new study compared MIRV with physician choice chemotherapy and found both a PFS and OS benefit in the MIRV arm. The results garnered significant enthusiasm from the audience, and others reacted positively as well.

“The results that she presented are just astounding, with a significant improvement in both progression-free and overall survival. I think certainly the overall survival needs to be highlighted here, because this is a patient population that’s notoriously difficult to treat,” said Ana Valente, MD, a gynecologic oncologist at the Ochsner Health System in New Orleans. Dr. Valente, who did not attend the presentation but was asked to comment on the study, is also a member of the Society of Gynecological Oncologist communications committee.

Unlike SORAYA, MIRASOL was open to patients who had not received bevacizumab, and Dr. Moore and colleagues found similar survival benefits in patients who had not received bevacizumab as in those who had, said Dr. Moore, who is the associate director of clinical research at Stephenson Cancer Center and director of the Oklahoma TSET Phase 1 Program, both in Oklahoma City. This opens the possibility of using MIRV instead of bevacizumab combined with chemotherapy in platinum-resistant patients.

“I think this data really shows you can move right to mirvetuximab [soravtansine] and feel pretty solid about the decision in a biomarker selected [population],” Dr. Moore said, during an interview.
 

Not just for high expression levels

MIRASOL was restricted to patients with high levels of expression of folate receptor–alpha, which is MIRV’s target on the surface of tumor cells. High expression is defined as at least 75% of viable tumor cells exhibiting a minimum of 2+ level membrane staining intensity by immunohistochemistry. That represents about 35% of patients, according to Dr. Moore, but she said that the drug also shows promise in patients with medium levels of folate receptor–alpha expression.

“I think it’s just going to be now starting to get those label extension studies launched to branch it out. Then you account for 60% of your population which [have] medium to high [expression levels], and that’s really where you see benefit,” said Dr. Moore. Medium expression levels of folate receptor–alpha are defined as 50% to greater than 75% of tumor cells with 2+ level membrane staining intensity.

She also noted that the FORWARD II trial combining mirvetuximab soravtansine with bevacizumab in platinum-resistant ovarian cancer is showing good results.

“We have really beautiful data [from FORWARD II]. If I have a medium expresser, I’m using the doublet [of MIRV and bevacizumab], and it works,” said Dr. Moore, while also pointing out that this remains an off-label use.

It’s possible that the drug could be extended even to low expression levels, defined as 25% to less than 50% of tumor cells with 2+ level membrane staining intensity. “[We are] currently working on that strategy with already available data,” said Dr. Moore.

She speculated that the improved OS may be attributed to the reduced toxicity of MIRV, compared with chemotherapy agents, which leaves patients feeling better and more able to pursue other treatments, which in turn may increase survival odds.

Dr. O’Cearbhaill touted the benefits of ADCs and their ability to target powerful cytotoxic agents while limiting side effects, and she is looking forward to more new therapies on the horizon.

“There are four [ADCs] in late stages of development [for platinum-resistant ovarian cancer], so hopefully there will be other ones coming online as well,” Dr. O’Cearbhaill said in an interview. “Then we’ll have to figure out how to sequence them, which drug will be best in class. Will we be just giving one or will be giving ADC followed by ADC?”
 

Study methods and results

The study enrolled 453 patients and randomized them to treatment with MIRV or investigator’s choice of chemotherapy, which could be paclitaxel, pegylated liposomal doxorubicin, or topotecan. The MIRV dose was 6 mg/kg adjusted ideal body weight every 3 weeks. The median age was 62 in the chemotherapy arm and 63 years in the MIRV arm. About 63% of the chemotherapy arm had prior bevacizumab exposure, as did 61% of the MIRV arm.

Median PFS was 5.62 months in the MIRV arm and 3.98 months in the chemotherapy arm (hazard ratio, 0.65; P less than .0001). The overall response rate was 42% in the MIRV arm and 16% in the chemotherapy arm (P < .0001).

The safety outcomes also favored MIRV: 42% experienced grade 3 or higher treatment-emergent adverse events (TEAEs) versus 54% in the chemotherapy group. Severe adverse events were also lower in MIRV, 24% versus 33%. Just 9% of patients in the MIRV discontinued because of TEAEs, compared with 16% in the chemotherapy arm.

MIRV was associated with blurred vision (41%), keratopathy (32%), and dry eye (28%), but these issues were generally manageable through collaboration with optometrists or ophthalmologists.

Dr. Moore and Dr. O’Cearbhaill reported receiving honoraria, research funding, and travel expenses from numerous pharmaceutical companies. Dr. O’Cearbhaill has consulted for or advised Aptitude Health, Bayer, Carina Biotech, Fresenius Kabi, GlaxoSmithKline, GOG Foundation, Immunogen, R-Pharm, Regeneron, and Seagen.

A new standard of care for patients with chemotherapy-naive persistent, recurrent, or metastatic cervical cancer is first-line therapy with the combination of the immune checkpoint inhibitor pembrolizumab (Keytruda) with platinum-based chemotherapy and paclitaxel – with or without bevacizumab.

This is based on final overall survival results from the phase 3, randomized KEYNOTE-826 study, which showed that adding immunotherapy resulted in a 40% reduction in risk of death, compared with chemotherapy alone, for women with advanced cervical cancers expressing programmed death–ligand 1 (PD-L1).

“At this protocol-specified final analysis of KEYNOTE-826, the addition of immune therapy to chemotherapy with or without the antiangiogenic bevacizumab showed substantial and clinically meaningful improvement in survival,” said lead author Bradley J. Monk, MD, from HonorHealth Research Institute, Phoenix.

He was speaking at a media briefing held prior to the annual meeting of the American Society of Clinical Oncology, where the results were presented.

“The results of this study solidify the addition of pembrolizumab to chemotherapy with or without bevacizumab in people with persistent, recurrent, or metastatic cervical cancer as the frontline standard of care for this disease. Survival significantly improved with this approach, regardless of PD-L1 expression, further supporting its use for all patients in this population,” commented ASCO expert Merry Jennifer Markham, MD, from the University of Florida, Gainesville.

At the briefing, Dr. Monk raised the possibility that adding immunotherapy to the standard of care could offer a chance for cure for some patients with advanced or recurrent cervical cancer.

“Is it possible to cure a widely metastatic cancer, a solid tumor? And I think it probably is,” he said. “There’s a tail to this [survival] curve, and I can’t believe that in my lifetime we as a group, as a team, have sort of figured out – and it’s not enough – that we can actually cure some patients, and if not maybe cure, have them at least live a long time, so it’s exciting.”

Briefing comoderater Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, agreed that the survival benefit “is exciting to see, and in my long career as a breast medical oncologist, I’m pretty sure we cure some metastatic breast cancer. We definitely had patients who lived out their normal life span and died of something else after decades.

“But the definition of cure, sadly, in these situations is that you die of something else without evidence of disease, so we certainly need to do better here and be better able to use the word ‘cure’ in the metastatic setting,” she added.
 

Promising start

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, and bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors had previously shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but KEYNOTE 826 was the first study to show a benefit to promoting immunotherapy to the front ranks.

In the first interim analysis of the trial, reported at the 2021 annual meeting of the European Society for Medical Oncology, after a median follow-up of 22 months, the combination of pembrolizumab and chemotherapy demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy plus placebo in a biomarker-selected population, which consisted of patients with a combined positive score (CPS) for PD-L1 of 1 or greater.

Pembrolizumab had no apparent efficacy in patients whose tumors did not have detectable PD-L1, however.
 

Latest results

Now the investigators are reporting the final analysis, conducted after a median follow-up of 39.1 months. The results are those for all comers (308 randomly assigned to receive pembrolizumab plus chemotherapy, and 309 assigned to receive chemotherapy plus placebo), as well as for the biomarker-selected population (consisting of all patients with PD-L1 CPS of 1 or greater) and for the subpopulation of patients with PD-L1 CPS of 10 or greater.

In the all-comers population, the median OS was 26.4 months for patients who received pembrolizumab, compared with 16.8 months for those who received placebo. The 24-month OS rates were 52.1% and 38.7%, respectively. The difference translated into a hazard ratio for death with pembrolizumab of 0.63 (P < .0001).

In the biomarker-selected population (273 assigned to pembrolizumab and 275 assigned to placebo), the respective median OS was 28.6 months versus 16.6 months, with 24-month OS rates of 53.5% versus 39.4%, which translates into an HR for death with pembrolizumab of 0.60 (P < .0001).

Not surprisingly, the best responses to the addition of the PD-1 inhibitor were seen among patients with a PD-L1 CPS of 10 or greater (158 assigned to pembrolizumab and 159 assigned to placebo). In this subgroup, the median OS was 29.6 months with the immune checkpoint inhibitor added to chemotherapy versus 17.4 months for chemotherapy plus placebo. The respective 24-month OS rates were 54.4% and 42.5%, and the HR for overall survival favoring pembrolizumab was 0.58 (P < .0001).

Median PFS 12-month PFS rates also favored pembrolizumab in both the total patient population and the biomarker-selected groups, with median PFS of approximately 10.4 months with pembrolizumab versus approximately 8.2 months with placebo.

The safety profile was manageable, with adverse events as expected from the safety profiles of the individual drugs in the combined regimen. No new safety signals have been seen since the interim analysis, Dr. Monk said.
 

Regimen details

Patients were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion. Approximately two-thirds of patients in each study arm received bevacizumab.

The dual primary endpoints of PFS and OS were each tested sequentially in patients with a PD-L1 CPS of 1 or greater in both the intention-to-treat or “all-comers” population and in patients with a PD-L1 CPS of 10 or greater.

Patient characteristics were generally well balanced between the treatment groups, except that a slightly higher proportion of patients in the pembrolizumab had tumors of squamous cell histology, compared with the placebo group (76.3% vs. 68.3%).

KEYNOTE-826 was funded by Merck. Dr. Monk has received honoraria and has participated in consulting/advising and speaker’s bureau activity with Merck and other companies. Dr. Gralow has had a consulting or advisory role with Genentech and Roche. Dr. Markham has had a consulting/advisory role for GlaxoSmithKline and has received institutional research funding from Merck and other companies.

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

A new standard of care for patients with chemotherapy-naive persistent, recurrent, or metastatic cervical cancer is first-line therapy with the combination of the immune checkpoint inhibitor pembrolizumab (Keytruda) with platinum-based chemotherapy and paclitaxel – with or without bevacizumab.

This is based on final overall survival results from the phase 3, randomized KEYNOTE-826 study, which showed that adding immunotherapy resulted in a 40% reduction in risk of death, compared with chemotherapy alone, for women with advanced cervical cancers expressing programmed death–ligand 1 (PD-L1).

“At this protocol-specified final analysis of KEYNOTE-826, the addition of immune therapy to chemotherapy with or without the antiangiogenic bevacizumab showed substantial and clinically meaningful improvement in survival,” said lead author Bradley J. Monk, MD, from HonorHealth Research Institute, Phoenix.

He was speaking at a media briefing held prior to the annual meeting of the American Society of Clinical Oncology, where the results were presented.

“The results of this study solidify the addition of pembrolizumab to chemotherapy with or without bevacizumab in people with persistent, recurrent, or metastatic cervical cancer as the frontline standard of care for this disease. Survival significantly improved with this approach, regardless of PD-L1 expression, further supporting its use for all patients in this population,” commented ASCO expert Merry Jennifer Markham, MD, from the University of Florida, Gainesville.

At the briefing, Dr. Monk raised the possibility that adding immunotherapy to the standard of care could offer a chance for cure for some patients with advanced or recurrent cervical cancer.

“Is it possible to cure a widely metastatic cancer, a solid tumor? And I think it probably is,” he said. “There’s a tail to this [survival] curve, and I can’t believe that in my lifetime we as a group, as a team, have sort of figured out – and it’s not enough – that we can actually cure some patients, and if not maybe cure, have them at least live a long time, so it’s exciting.”

Briefing comoderater Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, agreed that the survival benefit “is exciting to see, and in my long career as a breast medical oncologist, I’m pretty sure we cure some metastatic breast cancer. We definitely had patients who lived out their normal life span and died of something else after decades.

“But the definition of cure, sadly, in these situations is that you die of something else without evidence of disease, so we certainly need to do better here and be better able to use the word ‘cure’ in the metastatic setting,” she added.
 

Promising start

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, and bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors had previously shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but KEYNOTE 826 was the first study to show a benefit to promoting immunotherapy to the front ranks.

In the first interim analysis of the trial, reported at the 2021 annual meeting of the European Society for Medical Oncology, after a median follow-up of 22 months, the combination of pembrolizumab and chemotherapy demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy plus placebo in a biomarker-selected population, which consisted of patients with a combined positive score (CPS) for PD-L1 of 1 or greater.

Pembrolizumab had no apparent efficacy in patients whose tumors did not have detectable PD-L1, however.
 

Latest results

Now the investigators are reporting the final analysis, conducted after a median follow-up of 39.1 months. The results are those for all comers (308 randomly assigned to receive pembrolizumab plus chemotherapy, and 309 assigned to receive chemotherapy plus placebo), as well as for the biomarker-selected population (consisting of all patients with PD-L1 CPS of 1 or greater) and for the subpopulation of patients with PD-L1 CPS of 10 or greater.

In the all-comers population, the median OS was 26.4 months for patients who received pembrolizumab, compared with 16.8 months for those who received placebo. The 24-month OS rates were 52.1% and 38.7%, respectively. The difference translated into a hazard ratio for death with pembrolizumab of 0.63 (P < .0001).

In the biomarker-selected population (273 assigned to pembrolizumab and 275 assigned to placebo), the respective median OS was 28.6 months versus 16.6 months, with 24-month OS rates of 53.5% versus 39.4%, which translates into an HR for death with pembrolizumab of 0.60 (P < .0001).

Not surprisingly, the best responses to the addition of the PD-1 inhibitor were seen among patients with a PD-L1 CPS of 10 or greater (158 assigned to pembrolizumab and 159 assigned to placebo). In this subgroup, the median OS was 29.6 months with the immune checkpoint inhibitor added to chemotherapy versus 17.4 months for chemotherapy plus placebo. The respective 24-month OS rates were 54.4% and 42.5%, and the HR for overall survival favoring pembrolizumab was 0.58 (P < .0001).

Median PFS 12-month PFS rates also favored pembrolizumab in both the total patient population and the biomarker-selected groups, with median PFS of approximately 10.4 months with pembrolizumab versus approximately 8.2 months with placebo.

The safety profile was manageable, with adverse events as expected from the safety profiles of the individual drugs in the combined regimen. No new safety signals have been seen since the interim analysis, Dr. Monk said.
 

Regimen details

Patients were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion. Approximately two-thirds of patients in each study arm received bevacizumab.

The dual primary endpoints of PFS and OS were each tested sequentially in patients with a PD-L1 CPS of 1 or greater in both the intention-to-treat or “all-comers” population and in patients with a PD-L1 CPS of 10 or greater.

Patient characteristics were generally well balanced between the treatment groups, except that a slightly higher proportion of patients in the pembrolizumab had tumors of squamous cell histology, compared with the placebo group (76.3% vs. 68.3%).

KEYNOTE-826 was funded by Merck. Dr. Monk has received honoraria and has participated in consulting/advising and speaker’s bureau activity with Merck and other companies. Dr. Gralow has had a consulting or advisory role with Genentech and Roche. Dr. Markham has had a consulting/advisory role for GlaxoSmithKline and has received institutional research funding from Merck and other companies.

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

A new standard of care for patients with chemotherapy-naive persistent, recurrent, or metastatic cervical cancer is first-line therapy with the combination of the immune checkpoint inhibitor pembrolizumab (Keytruda) with platinum-based chemotherapy and paclitaxel – with or without bevacizumab.

This is based on final overall survival results from the phase 3, randomized KEYNOTE-826 study, which showed that adding immunotherapy resulted in a 40% reduction in risk of death, compared with chemotherapy alone, for women with advanced cervical cancers expressing programmed death–ligand 1 (PD-L1).

“At this protocol-specified final analysis of KEYNOTE-826, the addition of immune therapy to chemotherapy with or without the antiangiogenic bevacizumab showed substantial and clinically meaningful improvement in survival,” said lead author Bradley J. Monk, MD, from HonorHealth Research Institute, Phoenix.

He was speaking at a media briefing held prior to the annual meeting of the American Society of Clinical Oncology, where the results were presented.

“The results of this study solidify the addition of pembrolizumab to chemotherapy with or without bevacizumab in people with persistent, recurrent, or metastatic cervical cancer as the frontline standard of care for this disease. Survival significantly improved with this approach, regardless of PD-L1 expression, further supporting its use for all patients in this population,” commented ASCO expert Merry Jennifer Markham, MD, from the University of Florida, Gainesville.

At the briefing, Dr. Monk raised the possibility that adding immunotherapy to the standard of care could offer a chance for cure for some patients with advanced or recurrent cervical cancer.

“Is it possible to cure a widely metastatic cancer, a solid tumor? And I think it probably is,” he said. “There’s a tail to this [survival] curve, and I can’t believe that in my lifetime we as a group, as a team, have sort of figured out – and it’s not enough – that we can actually cure some patients, and if not maybe cure, have them at least live a long time, so it’s exciting.”

Briefing comoderater Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, agreed that the survival benefit “is exciting to see, and in my long career as a breast medical oncologist, I’m pretty sure we cure some metastatic breast cancer. We definitely had patients who lived out their normal life span and died of something else after decades.

“But the definition of cure, sadly, in these situations is that you die of something else without evidence of disease, so we certainly need to do better here and be better able to use the word ‘cure’ in the metastatic setting,” she added.
 

Promising start

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, and bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors had previously shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but KEYNOTE 826 was the first study to show a benefit to promoting immunotherapy to the front ranks.

In the first interim analysis of the trial, reported at the 2021 annual meeting of the European Society for Medical Oncology, after a median follow-up of 22 months, the combination of pembrolizumab and chemotherapy demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy plus placebo in a biomarker-selected population, which consisted of patients with a combined positive score (CPS) for PD-L1 of 1 or greater.

Pembrolizumab had no apparent efficacy in patients whose tumors did not have detectable PD-L1, however.
 

Latest results

Now the investigators are reporting the final analysis, conducted after a median follow-up of 39.1 months. The results are those for all comers (308 randomly assigned to receive pembrolizumab plus chemotherapy, and 309 assigned to receive chemotherapy plus placebo), as well as for the biomarker-selected population (consisting of all patients with PD-L1 CPS of 1 or greater) and for the subpopulation of patients with PD-L1 CPS of 10 or greater.

In the all-comers population, the median OS was 26.4 months for patients who received pembrolizumab, compared with 16.8 months for those who received placebo. The 24-month OS rates were 52.1% and 38.7%, respectively. The difference translated into a hazard ratio for death with pembrolizumab of 0.63 (P < .0001).

In the biomarker-selected population (273 assigned to pembrolizumab and 275 assigned to placebo), the respective median OS was 28.6 months versus 16.6 months, with 24-month OS rates of 53.5% versus 39.4%, which translates into an HR for death with pembrolizumab of 0.60 (P < .0001).

Not surprisingly, the best responses to the addition of the PD-1 inhibitor were seen among patients with a PD-L1 CPS of 10 or greater (158 assigned to pembrolizumab and 159 assigned to placebo). In this subgroup, the median OS was 29.6 months with the immune checkpoint inhibitor added to chemotherapy versus 17.4 months for chemotherapy plus placebo. The respective 24-month OS rates were 54.4% and 42.5%, and the HR for overall survival favoring pembrolizumab was 0.58 (P < .0001).

Median PFS 12-month PFS rates also favored pembrolizumab in both the total patient population and the biomarker-selected groups, with median PFS of approximately 10.4 months with pembrolizumab versus approximately 8.2 months with placebo.

The safety profile was manageable, with adverse events as expected from the safety profiles of the individual drugs in the combined regimen. No new safety signals have been seen since the interim analysis, Dr. Monk said.
 

Regimen details

Patients were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion. Approximately two-thirds of patients in each study arm received bevacizumab.

The dual primary endpoints of PFS and OS were each tested sequentially in patients with a PD-L1 CPS of 1 or greater in both the intention-to-treat or “all-comers” population and in patients with a PD-L1 CPS of 10 or greater.

Patient characteristics were generally well balanced between the treatment groups, except that a slightly higher proportion of patients in the pembrolizumab had tumors of squamous cell histology, compared with the placebo group (76.3% vs. 68.3%).

KEYNOTE-826 was funded by Merck. Dr. Monk has received honoraria and has participated in consulting/advising and speaker’s bureau activity with Merck and other companies. Dr. Gralow has had a consulting or advisory role with Genentech and Roche. Dr. Markham has had a consulting/advisory role for GlaxoSmithKline and has received institutional research funding from Merck and other companies.

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

CHICAGO – New results in the treatment of advanced ovarian cancer have been welcomed by an expert not involved in the trial, even though the study showed only an improvement in progression-free survival (PFS), not yet overall survival.

The results come from the DUO-O trial, in which the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza) and immunotherapy with the anti–PD-L1 antibody durvalumab (Imfinzi) were added on to standard of care with paclitaxel/carboplatin chemotherapy and bevacizumab (Avastin) in patients with newly diagnosed,non–BRCA-mutated advanced ovarian cancer.

A preplanned interim analysis revealed that the addition of durvalumab and olaparib was associated with a 37% improvement of PFS, compared with the standard of care of chemotherapy plus bevacizumab alone.

This improvement increased to 51% in patients who had tumors positive for homologous recombination deficiency (HRD), which indicates the inability to effectively repair double-stranded DNA breaks, a defect that is present in approximately 70% of ovarian cancers.

Coprincipal investigator Carol Aghajanian, MD, chief of the gynecologic medical oncology service at Memorial Sloan Kettering Cancer Center, New York, described the benefit seen with the novel combination therapy as both “statistically significant and clinically meaningful.”

She was speaking at a press briefing held ahead of the annual meeting of the American Society of Clinical Oncology, where the results were presented.

Commenting for ASCO, Merry Jennifer Markham, MD, professor of medicine and chief of the division of hematology and oncology at University of Florida Health, Gainesville, said the results represents a “huge step forward.”

She added the rate of progress it represents may not be “quick enough for our patients with advanced ovarian cancer but every little integral improvement that we can find in studies that are important, like this one, really means so much to that individual patient in that exam room.”

Dr. Markham underlined that around 80% of women with epithelial ovarian cancer are diagnosed at an advanced stage. “They know what they are facing,” she said. “The vast majority” of them will have a recurrence “at some point.”

“So while progression-free survival may not necessarily mean their overall survival, there will be hope it does. And I’m very excited to see where this study heads in that direction.” Dr. Markham added that PFS is “very important to our patients,” and the study does represent progress. “We are chipping away at improving outcomes for advanced ovarian cancer.”

Moreover, “women are often disappointed when their tumor doesn’t have a BRCA mutation because they know that that may limit some of their treatment options,” and so the current study suggests that there are “options for all-comers” and “there is still hope.”
 

Access to treatment and testing

When asked whether there could be any access issues for patients clinically eligible for the novel combination, Dr. Aghajanian said that all of the drugs have been approved by the Food and Drug Administration for indications that cover this usage.

They are also covered by medical insurance and, for those patients with financial toxicity, “there is access to co-pay assistance programs and the like.”

She said that patients can then “be counseled on their expected benefit,” based on their BRCA and HRD testing.

Dr. Markham, on the other hand, said she is “a little less optimistic” about access, explaining that she practices in the southern United States, and “our populations [and] insurance coverages are a bit different.”

She noted that, at her institution, a “fair number of patients are underinsured,” and they “ran into a lot of issues with people not being able to afford their copays,” which can be “prohibitive.”

“A large portion of my counseling has been and will continue to be around the benefit, but also the financial toxicity, that that individual patient may experience and the need for copay assistance programs or other support mechanisms,” Markham said.

Dr. Aghajanian added that “financial toxicity and the access issue comes even prior to the treatment, in getting those BRCA1/2 tests and the HRD testing done, so patients have the information they need to make informed decisions.”

“We do have disparities with genetic testing and genomic testing that need to be solved,” she said.
 

Study details

Previous studies, including SOLO1 and PAOLA-1, have shown that maintenance therapy with olaparib and bevacizumab improves outcomes in the first-line treatment of advanced ovarian cancer.

“However, there still remains unmet need, especially in some patient subgroups without a BRCA mutation,” Dr. Aghajanian said.

While the addition of immunotherapy to standard of care has yet to show a clinical benefit in this setting in phase 3 trials, the phase 2 MEDIOLA study indicated that the combination of durvalumab, bevacizumab, and olaparib was active in nongermline, BRCA-mutated, platinum-sensitive relapsed cancer.

The phase 3 DUO-O study therefore set out to determine whether this combination would be beneficial as a maintenance therapy in 1130 patients with newly diagnosed stage III or IV high-grade ovarian cancer without a tumor BRCA1/2 mutation.

Patients were required to have had no prior systemic therapy for ovarian cancer, and be naive to both PARP inhibition and immunotherapy. They also had to have completed up-front primary debulking surgery, or be scheduled to undergo the procedure.

After an initial cycle of paclitaxel/carboplatin chemotherapy, the patients were randomly assigned to one of three regimens:

• Standard of care treatment, comprising chemotherapy plus bevacizumab and durvalumab-placebo, followed by maintenance therapy with bevacizumab, durvalumab-placebo, and olaparib-placebo (arm 1)
• Chemotherapy plus bevacizumab and durvalumab, followed by maintenance therapy with bevacizumab, durvalumab, and olaparib-placebo (arm 2)
• Chemotherapy plus bevacizumab and durvalumab, followed by maintenance therapy with bevacizumab, durvalumab, and olaparib (arm 3)

In the maintenance phase, bevacizumab was to be given for a total of 15 months, while durvalumab and olaparib, or their equivalent placebos, were prescribed for 24 months. Treatment was continued until disease progression, study completion, or another discontinuation criteria was met.

Dr. Aghajanian presented results from a preplanned interim analysis, with a date cutoff of Dec. 5, 2022.

Among HRD-positive patients, those in arm 3 had a significantly longer PFS than those in arm 1, at a median of 37.3 months versus 23 months, or a hazard ratio of 0.49 (P < .0001).

In the intention-to-treat analysis, arm 3 was also associated with a significant improvement in median PFS over arm 1, at 24.2 months versus 19.3 months, or an HR of 0.63 (P < .0001), indicating that the trial met both of its primary endpoints.

While there was a numerical difference in median PFS between arm 2 and arm 1, at a median of 20.6 months versus 19.3 months, this was not significant. This means that relative contribution of adding durvalumab alone is not clear, Dr. Aghajanian commented, and said that this comparison “will be reassessed at the time of the final PFS analysis.”

She added that a “PFS effect was observed across all subgroups for the arm 3 versus arm 1 comparison,” including in the HRD-negative subgroup, at a median of 20.9 months versus 17.4 months, or an HR of 0.68.

The safety and tolerability of the regimens were generally consistent with what is known for the individual agents, she commented.

Serious adverse events were reported in 34%, 43%, and 39% of patients in arms 1, 2, and 3, respectively.

The most common grade 3 or higher adverse events were neutropenia (in 26% of arm 1 patients, 28% of those in arm 2, and 31% of those in arm 3) followed by anemia (in 8%, 8%, and 24%, respectively).

Dose modifications were required in 72% of arm 1 patients, 80% of those in arm 2, and 85% of arm 3 patients. Treatment discontinuation was recorded in 20%, 26%, and 35%, respectively.
 

Tackling underserved patient populations

Discussing the results, Christina Fotopoulou, MD, PhD, professor of gynecological cancer surgery in the department of surgery and cancer, Imperial College London, said that, while the regimen may seem new, the treatments involved are “veterans,” and that they are nevertheless tackling previously underserved patient populations.

Dr. Fotopoulou, who was not involved in the study, noted that the results were highly anticipated, and the study has delivered a “breakthrough in ovarian cancer.” She nevertheless questioned the choice of the control arm, and pointed out that the hazard ratio in favor of the combination therapy is “relatively modest” considering that it involves three drugs.

Dr. Fotopoulou highlighted, however, that one of the most important results was in the HRD-negative patients, which she characterized as the equivalent of the clinicians going to “the dark side of the moon.” She said that “for the first time, we have a positive study in this patient population,” although she underlined that the results are from an interim analysis.

The key question that remains, Dr. Fotopoulou asked, is “why? What is making the difference?” She noted that, unfortunately, the trial design does not allow the identification of the relative contribution of olaparib and durvalumab.

The study was sponsored by AstraZeneca, and conducted in collaboration with the European Network of Gynaecological Oncological Trial Groups, GOG Foundation, and Myriad Genetic Laboratories. Dr. Aghajanian declared relationships with AstraZeneca, Merck, Eisai, Repare Therapeutics, AbbVie, Clovis Oncology, and Genentech/Roche. Dr. Markham declared relationships with Pfizer, GlaxoSmithKline, Aduro Biotech, Lilly, Tesaro, Novartis, VBL Therapeutics, AstraZeneca, and Merck.

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

CHICAGO – New results in the treatment of advanced ovarian cancer have been welcomed by an expert not involved in the trial, even though the study showed only an improvement in progression-free survival (PFS), not yet overall survival.

The results come from the DUO-O trial, in which the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza) and immunotherapy with the anti–PD-L1 antibody durvalumab (Imfinzi) were added on to standard of care with paclitaxel/carboplatin chemotherapy and bevacizumab (Avastin) in patients with newly diagnosed,non–BRCA-mutated advanced ovarian cancer.

A preplanned interim analysis revealed that the addition of durvalumab and olaparib was associated with a 37% improvement of PFS, compared with the standard of care of chemotherapy plus bevacizumab alone.

This improvement increased to 51% in patients who had tumors positive for homologous recombination deficiency (HRD), which indicates the inability to effectively repair double-stranded DNA breaks, a defect that is present in approximately 70% of ovarian cancers.

Coprincipal investigator Carol Aghajanian, MD, chief of the gynecologic medical oncology service at Memorial Sloan Kettering Cancer Center, New York, described the benefit seen with the novel combination therapy as both “statistically significant and clinically meaningful.”

She was speaking at a press briefing held ahead of the annual meeting of the American Society of Clinical Oncology, where the results were presented.

Commenting for ASCO, Merry Jennifer Markham, MD, professor of medicine and chief of the division of hematology and oncology at University of Florida Health, Gainesville, said the results represents a “huge step forward.”

She added the rate of progress it represents may not be “quick enough for our patients with advanced ovarian cancer but every little integral improvement that we can find in studies that are important, like this one, really means so much to that individual patient in that exam room.”

Dr. Markham underlined that around 80% of women with epithelial ovarian cancer are diagnosed at an advanced stage. “They know what they are facing,” she said. “The vast majority” of them will have a recurrence “at some point.”

“So while progression-free survival may not necessarily mean their overall survival, there will be hope it does. And I’m very excited to see where this study heads in that direction.” Dr. Markham added that PFS is “very important to our patients,” and the study does represent progress. “We are chipping away at improving outcomes for advanced ovarian cancer.”

Moreover, “women are often disappointed when their tumor doesn’t have a BRCA mutation because they know that that may limit some of their treatment options,” and so the current study suggests that there are “options for all-comers” and “there is still hope.”
 

Access to treatment and testing

When asked whether there could be any access issues for patients clinically eligible for the novel combination, Dr. Aghajanian said that all of the drugs have been approved by the Food and Drug Administration for indications that cover this usage.

They are also covered by medical insurance and, for those patients with financial toxicity, “there is access to co-pay assistance programs and the like.”

She said that patients can then “be counseled on their expected benefit,” based on their BRCA and HRD testing.

Dr. Markham, on the other hand, said she is “a little less optimistic” about access, explaining that she practices in the southern United States, and “our populations [and] insurance coverages are a bit different.”

She noted that, at her institution, a “fair number of patients are underinsured,” and they “ran into a lot of issues with people not being able to afford their copays,” which can be “prohibitive.”

“A large portion of my counseling has been and will continue to be around the benefit, but also the financial toxicity, that that individual patient may experience and the need for copay assistance programs or other support mechanisms,” Markham said.

Dr. Aghajanian added that “financial toxicity and the access issue comes even prior to the treatment, in getting those BRCA1/2 tests and the HRD testing done, so patients have the information they need to make informed decisions.”

“We do have disparities with genetic testing and genomic testing that need to be solved,” she said.
 

Study details

Previous studies, including SOLO1 and PAOLA-1, have shown that maintenance therapy with olaparib and bevacizumab improves outcomes in the first-line treatment of advanced ovarian cancer.

“However, there still remains unmet need, especially in some patient subgroups without a BRCA mutation,” Dr. Aghajanian said.

While the addition of immunotherapy to standard of care has yet to show a clinical benefit in this setting in phase 3 trials, the phase 2 MEDIOLA study indicated that the combination of durvalumab, bevacizumab, and olaparib was active in nongermline, BRCA-mutated, platinum-sensitive relapsed cancer.

The phase 3 DUO-O study therefore set out to determine whether this combination would be beneficial as a maintenance therapy in 1130 patients with newly diagnosed stage III or IV high-grade ovarian cancer without a tumor BRCA1/2 mutation.

Patients were required to have had no prior systemic therapy for ovarian cancer, and be naive to both PARP inhibition and immunotherapy. They also had to have completed up-front primary debulking surgery, or be scheduled to undergo the procedure.

After an initial cycle of paclitaxel/carboplatin chemotherapy, the patients were randomly assigned to one of three regimens:

• Standard of care treatment, comprising chemotherapy plus bevacizumab and durvalumab-placebo, followed by maintenance therapy with bevacizumab, durvalumab-placebo, and olaparib-placebo (arm 1)
• Chemotherapy plus bevacizumab and durvalumab, followed by maintenance therapy with bevacizumab, durvalumab, and olaparib-placebo (arm 2)
• Chemotherapy plus bevacizumab and durvalumab, followed by maintenance therapy with bevacizumab, durvalumab, and olaparib (arm 3)

In the maintenance phase, bevacizumab was to be given for a total of 15 months, while durvalumab and olaparib, or their equivalent placebos, were prescribed for 24 months. Treatment was continued until disease progression, study completion, or another discontinuation criteria was met.

Dr. Aghajanian presented results from a preplanned interim analysis, with a date cutoff of Dec. 5, 2022.

Among HRD-positive patients, those in arm 3 had a significantly longer PFS than those in arm 1, at a median of 37.3 months versus 23 months, or a hazard ratio of 0.49 (P < .0001).

In the intention-to-treat analysis, arm 3 was also associated with a significant improvement in median PFS over arm 1, at 24.2 months versus 19.3 months, or an HR of 0.63 (P < .0001), indicating that the trial met both of its primary endpoints.

While there was a numerical difference in median PFS between arm 2 and arm 1, at a median of 20.6 months versus 19.3 months, this was not significant. This means that relative contribution of adding durvalumab alone is not clear, Dr. Aghajanian commented, and said that this comparison “will be reassessed at the time of the final PFS analysis.”

She added that a “PFS effect was observed across all subgroups for the arm 3 versus arm 1 comparison,” including in the HRD-negative subgroup, at a median of 20.9 months versus 17.4 months, or an HR of 0.68.

The safety and tolerability of the regimens were generally consistent with what is known for the individual agents, she commented.

Serious adverse events were reported in 34%, 43%, and 39% of patients in arms 1, 2, and 3, respectively.

The most common grade 3 or higher adverse events were neutropenia (in 26% of arm 1 patients, 28% of those in arm 2, and 31% of those in arm 3) followed by anemia (in 8%, 8%, and 24%, respectively).

Dose modifications were required in 72% of arm 1 patients, 80% of those in arm 2, and 85% of arm 3 patients. Treatment discontinuation was recorded in 20%, 26%, and 35%, respectively.
 

Tackling underserved patient populations

Discussing the results, Christina Fotopoulou, MD, PhD, professor of gynecological cancer surgery in the department of surgery and cancer, Imperial College London, said that, while the regimen may seem new, the treatments involved are “veterans,” and that they are nevertheless tackling previously underserved patient populations.

Dr. Fotopoulou, who was not involved in the study, noted that the results were highly anticipated, and the study has delivered a “breakthrough in ovarian cancer.” She nevertheless questioned the choice of the control arm, and pointed out that the hazard ratio in favor of the combination therapy is “relatively modest” considering that it involves three drugs.

Dr. Fotopoulou highlighted, however, that one of the most important results was in the HRD-negative patients, which she characterized as the equivalent of the clinicians going to “the dark side of the moon.” She said that “for the first time, we have a positive study in this patient population,” although she underlined that the results are from an interim analysis.

The key question that remains, Dr. Fotopoulou asked, is “why? What is making the difference?” She noted that, unfortunately, the trial design does not allow the identification of the relative contribution of olaparib and durvalumab.

The study was sponsored by AstraZeneca, and conducted in collaboration with the European Network of Gynaecological Oncological Trial Groups, GOG Foundation, and Myriad Genetic Laboratories. Dr. Aghajanian declared relationships with AstraZeneca, Merck, Eisai, Repare Therapeutics, AbbVie, Clovis Oncology, and Genentech/Roche. Dr. Markham declared relationships with Pfizer, GlaxoSmithKline, Aduro Biotech, Lilly, Tesaro, Novartis, VBL Therapeutics, AstraZeneca, and Merck.

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

CHICAGO – New results in the treatment of advanced ovarian cancer have been welcomed by an expert not involved in the trial, even though the study showed only an improvement in progression-free survival (PFS), not yet overall survival.

The results come from the DUO-O trial, in which the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza) and immunotherapy with the anti–PD-L1 antibody durvalumab (Imfinzi) were added on to standard of care with paclitaxel/carboplatin chemotherapy and bevacizumab (Avastin) in patients with newly diagnosed,non–BRCA-mutated advanced ovarian cancer.

A preplanned interim analysis revealed that the addition of durvalumab and olaparib was associated with a 37% improvement of PFS, compared with the standard of care of chemotherapy plus bevacizumab alone.

This improvement increased to 51% in patients who had tumors positive for homologous recombination deficiency (HRD), which indicates the inability to effectively repair double-stranded DNA breaks, a defect that is present in approximately 70% of ovarian cancers.

Coprincipal investigator Carol Aghajanian, MD, chief of the gynecologic medical oncology service at Memorial Sloan Kettering Cancer Center, New York, described the benefit seen with the novel combination therapy as both “statistically significant and clinically meaningful.”

She was speaking at a press briefing held ahead of the annual meeting of the American Society of Clinical Oncology, where the results were presented.

Commenting for ASCO, Merry Jennifer Markham, MD, professor of medicine and chief of the division of hematology and oncology at University of Florida Health, Gainesville, said the results represents a “huge step forward.”

She added the rate of progress it represents may not be “quick enough for our patients with advanced ovarian cancer but every little integral improvement that we can find in studies that are important, like this one, really means so much to that individual patient in that exam room.”

Dr. Markham underlined that around 80% of women with epithelial ovarian cancer are diagnosed at an advanced stage. “They know what they are facing,” she said. “The vast majority” of them will have a recurrence “at some point.”

“So while progression-free survival may not necessarily mean their overall survival, there will be hope it does. And I’m very excited to see where this study heads in that direction.” Dr. Markham added that PFS is “very important to our patients,” and the study does represent progress. “We are chipping away at improving outcomes for advanced ovarian cancer.”

Moreover, “women are often disappointed when their tumor doesn’t have a BRCA mutation because they know that that may limit some of their treatment options,” and so the current study suggests that there are “options for all-comers” and “there is still hope.”
 

Access to treatment and testing

When asked whether there could be any access issues for patients clinically eligible for the novel combination, Dr. Aghajanian said that all of the drugs have been approved by the Food and Drug Administration for indications that cover this usage.

They are also covered by medical insurance and, for those patients with financial toxicity, “there is access to co-pay assistance programs and the like.”

She said that patients can then “be counseled on their expected benefit,” based on their BRCA and HRD testing.

Dr. Markham, on the other hand, said she is “a little less optimistic” about access, explaining that she practices in the southern United States, and “our populations [and] insurance coverages are a bit different.”

She noted that, at her institution, a “fair number of patients are underinsured,” and they “ran into a lot of issues with people not being able to afford their copays,” which can be “prohibitive.”

“A large portion of my counseling has been and will continue to be around the benefit, but also the financial toxicity, that that individual patient may experience and the need for copay assistance programs or other support mechanisms,” Markham said.

Dr. Aghajanian added that “financial toxicity and the access issue comes even prior to the treatment, in getting those BRCA1/2 tests and the HRD testing done, so patients have the information they need to make informed decisions.”

“We do have disparities with genetic testing and genomic testing that need to be solved,” she said.
 

Study details

Previous studies, including SOLO1 and PAOLA-1, have shown that maintenance therapy with olaparib and bevacizumab improves outcomes in the first-line treatment of advanced ovarian cancer.

“However, there still remains unmet need, especially in some patient subgroups without a BRCA mutation,” Dr. Aghajanian said.

While the addition of immunotherapy to standard of care has yet to show a clinical benefit in this setting in phase 3 trials, the phase 2 MEDIOLA study indicated that the combination of durvalumab, bevacizumab, and olaparib was active in nongermline, BRCA-mutated, platinum-sensitive relapsed cancer.

The phase 3 DUO-O study therefore set out to determine whether this combination would be beneficial as a maintenance therapy in 1130 patients with newly diagnosed stage III or IV high-grade ovarian cancer without a tumor BRCA1/2 mutation.

Patients were required to have had no prior systemic therapy for ovarian cancer, and be naive to both PARP inhibition and immunotherapy. They also had to have completed up-front primary debulking surgery, or be scheduled to undergo the procedure.

After an initial cycle of paclitaxel/carboplatin chemotherapy, the patients were randomly assigned to one of three regimens:

• Standard of care treatment, comprising chemotherapy plus bevacizumab and durvalumab-placebo, followed by maintenance therapy with bevacizumab, durvalumab-placebo, and olaparib-placebo (arm 1)
• Chemotherapy plus bevacizumab and durvalumab, followed by maintenance therapy with bevacizumab, durvalumab, and olaparib-placebo (arm 2)
• Chemotherapy plus bevacizumab and durvalumab, followed by maintenance therapy with bevacizumab, durvalumab, and olaparib (arm 3)

In the maintenance phase, bevacizumab was to be given for a total of 15 months, while durvalumab and olaparib, or their equivalent placebos, were prescribed for 24 months. Treatment was continued until disease progression, study completion, or another discontinuation criteria was met.

Dr. Aghajanian presented results from a preplanned interim analysis, with a date cutoff of Dec. 5, 2022.

Among HRD-positive patients, those in arm 3 had a significantly longer PFS than those in arm 1, at a median of 37.3 months versus 23 months, or a hazard ratio of 0.49 (P < .0001).

In the intention-to-treat analysis, arm 3 was also associated with a significant improvement in median PFS over arm 1, at 24.2 months versus 19.3 months, or an HR of 0.63 (P < .0001), indicating that the trial met both of its primary endpoints.

While there was a numerical difference in median PFS between arm 2 and arm 1, at a median of 20.6 months versus 19.3 months, this was not significant. This means that relative contribution of adding durvalumab alone is not clear, Dr. Aghajanian commented, and said that this comparison “will be reassessed at the time of the final PFS analysis.”

She added that a “PFS effect was observed across all subgroups for the arm 3 versus arm 1 comparison,” including in the HRD-negative subgroup, at a median of 20.9 months versus 17.4 months, or an HR of 0.68.

The safety and tolerability of the regimens were generally consistent with what is known for the individual agents, she commented.

Serious adverse events were reported in 34%, 43%, and 39% of patients in arms 1, 2, and 3, respectively.

The most common grade 3 or higher adverse events were neutropenia (in 26% of arm 1 patients, 28% of those in arm 2, and 31% of those in arm 3) followed by anemia (in 8%, 8%, and 24%, respectively).

Dose modifications were required in 72% of arm 1 patients, 80% of those in arm 2, and 85% of arm 3 patients. Treatment discontinuation was recorded in 20%, 26%, and 35%, respectively.
 

Tackling underserved patient populations

Discussing the results, Christina Fotopoulou, MD, PhD, professor of gynecological cancer surgery in the department of surgery and cancer, Imperial College London, said that, while the regimen may seem new, the treatments involved are “veterans,” and that they are nevertheless tackling previously underserved patient populations.

Dr. Fotopoulou, who was not involved in the study, noted that the results were highly anticipated, and the study has delivered a “breakthrough in ovarian cancer.” She nevertheless questioned the choice of the control arm, and pointed out that the hazard ratio in favor of the combination therapy is “relatively modest” considering that it involves three drugs.

Dr. Fotopoulou highlighted, however, that one of the most important results was in the HRD-negative patients, which she characterized as the equivalent of the clinicians going to “the dark side of the moon.” She said that “for the first time, we have a positive study in this patient population,” although she underlined that the results are from an interim analysis.

The key question that remains, Dr. Fotopoulou asked, is “why? What is making the difference?” She noted that, unfortunately, the trial design does not allow the identification of the relative contribution of olaparib and durvalumab.

The study was sponsored by AstraZeneca, and conducted in collaboration with the European Network of Gynaecological Oncological Trial Groups, GOG Foundation, and Myriad Genetic Laboratories. Dr. Aghajanian declared relationships with AstraZeneca, Merck, Eisai, Repare Therapeutics, AbbVie, Clovis Oncology, and Genentech/Roche. Dr. Markham declared relationships with Pfizer, GlaxoSmithKline, Aduro Biotech, Lilly, Tesaro, Novartis, VBL Therapeutics, AstraZeneca, and Merck.

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

CHICAGO – When it comes to preventing pelvic recurrence in low-risk cervical cancer, simple hysterectomy is not inferior to radical hysterectomy, according to results from a phase 3, randomized, controlled trial.

“Following adequate and rigorous preoperative assessment, and that’s key – very careful [patient selection] – simple hysterectomies can now be considered the new standard of care for patients with low-risk early-stage cervical cancer,” said Marie Plante, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. A simple hysterectomy removes the uterus and cervix, while a radical hysterectomy also removes the parametrium and upper vagina.

Cervical cancer incidence has gone down over the past 2 decades as a result of improved screening, and patients tend to be lower in age and are more likely to have low-risk, early-stage disease, according to Dr. Plante. “Although radical surgery is highly effective for the treatment of low-risk disease, women are at risk of suffering survivorship issues related to long-term surgical side effects including compromised bladder, bowel, and sexual function,” said Dr. Plante, who is a professor of obstetrics and gynecology at Laval University and head of clinical research at l’Hôtel-Dieu de Québec, both in Quebec City.

Retrospective studies found that infiltration of the parametrium is quite rare in low-risk cases, “suggesting that less radical surgery may be a safe option associated with decreased morbidity – what we call surgical de-escalation,” said Dr. Plante.

To test that idea more rigorously, the researchers designed the SHAPE trial, which randomized 700 women to a simple hysterectomy or radical hysterectomy. Patients were carefully selected to be low risk, having squamous cell, adenocarcinoma, or adenosquamous carcinoma, stage IA2 or IB2 tumors, fewer than 10 mm of stromal invasion on loop electrosurgical excision procedure or cone biopsy, less than 50% stromal invasion seen in MRI, and a maximum tumor dimension of 20 mm or less. Tumors were grade I-III or not assessable.

Over a median follow-up of 4.5 years, pelvic recurrence was 2.52% in the simple hysterectomy group and 2.17% in the radical hysterectomy group. The difference between the recurrence rate between the two groups was 0.35%, with an upper 95% confidence limit of 2.32%, below the threshold of 4% which had been predetermined as a benchmark for similar outcomes between the two groups. “Therefore, noninferiority of simple hysterectomy to radical hysterectomy could be concluded,” said Dr. Plante.

There were no statistically significant differences in intraoperative complications or mortality between the groups.
 

Surgery-related adverse events greater in radical hysterectomy group

There were some differences between the groups with respect to surgery-related adverse events. Within 4 weeks of surgery, there was a greater incidence of any adverse event in the radical hysterectomy group (50.6% vs. 42.6%; P = .04), as well as greater incidences of urinary incontinence (5.5% vs. 2.4%; P = .048) and urinary retention (11.0% vs. 0.6%; P < .0001). In the 4 weeks following surgery, there was a trend toward more surgery-related adverse events in the radical hysterectomy group (60.5% vs. 53.6%; P = .08) and higher incidences of urinary incontinence (11.0% vs. 4.7%; P = .003) and urinary retention (9.9% vs. 0.6%; P < .0001).

“Urinary incontinence and urinary retention are statistically worse in the radical hysterectomy group – both acutely, as well as [during] the following four weeks after surgery, suggesting that the problem persisted over time,” said Dr. Plante.

Dr. Plante also presented the study at a premeeting virtual press conference, during which Kathleen Moore, MD, provided comments on the study. She expressed enthusiasm about the results.

“Amongst those carefully selected tumors, radical hysterectomy can be converted to a simple hysterectomy, including minimally invasive. You still have to do nodes – that’s an important thing to remember – but you can do this without loss of oncologic control. And importantly, with reduction in surgical complications, postop morbidity, specifically neurologic morbidity. The moment this is presented [at the ASCO conference] this will be the new standard of care, and it represents a huge step forward in the care of women with early-stage cervical cancer,” said Dr. Moore, who is a professor of gynecologic oncology at the University of Oklahoma Health Sciences Center, Oklahoma City.

Also in the press conference, Dr. Plante emphasized the importance of a thorough understanding of the tumor, including size, imaging, and pathology. “The more conservative one wants to be, the more meticulous, the more careful one has to be to make sure that we’re truly dealing with low-risk patients.”

During the question-and-answer session following her presentation at the ASCO session, a moderator asked Dr. Plante if the presence of lymph vascular space invasion (LVSI) should prompt a radical hysterectomy.

Dr. Plante noted that about 13% of both radical and simple hysterectomy groups had LVSI present. “I think the key thing is careful selection, but I’m not sure that we should exclude LVSI [from consideration for simple hysterectomy] de facto,” she said.

Dr. Plante has consulted or advised Merck Serono and has received travel, accommodations, or other expenses from AstraZeneca. Dr. Moore has consulted, advised, and received research funding and travel expenses from numerous pharmaceutical companies.

CHICAGO – When it comes to preventing pelvic recurrence in low-risk cervical cancer, simple hysterectomy is not inferior to radical hysterectomy, according to results from a phase 3, randomized, controlled trial.

“Following adequate and rigorous preoperative assessment, and that’s key – very careful [patient selection] – simple hysterectomies can now be considered the new standard of care for patients with low-risk early-stage cervical cancer,” said Marie Plante, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. A simple hysterectomy removes the uterus and cervix, while a radical hysterectomy also removes the parametrium and upper vagina.

Cervical cancer incidence has gone down over the past 2 decades as a result of improved screening, and patients tend to be lower in age and are more likely to have low-risk, early-stage disease, according to Dr. Plante. “Although radical surgery is highly effective for the treatment of low-risk disease, women are at risk of suffering survivorship issues related to long-term surgical side effects including compromised bladder, bowel, and sexual function,” said Dr. Plante, who is a professor of obstetrics and gynecology at Laval University and head of clinical research at l’Hôtel-Dieu de Québec, both in Quebec City.

Retrospective studies found that infiltration of the parametrium is quite rare in low-risk cases, “suggesting that less radical surgery may be a safe option associated with decreased morbidity – what we call surgical de-escalation,” said Dr. Plante.

To test that idea more rigorously, the researchers designed the SHAPE trial, which randomized 700 women to a simple hysterectomy or radical hysterectomy. Patients were carefully selected to be low risk, having squamous cell, adenocarcinoma, or adenosquamous carcinoma, stage IA2 or IB2 tumors, fewer than 10 mm of stromal invasion on loop electrosurgical excision procedure or cone biopsy, less than 50% stromal invasion seen in MRI, and a maximum tumor dimension of 20 mm or less. Tumors were grade I-III or not assessable.

Over a median follow-up of 4.5 years, pelvic recurrence was 2.52% in the simple hysterectomy group and 2.17% in the radical hysterectomy group. The difference between the recurrence rate between the two groups was 0.35%, with an upper 95% confidence limit of 2.32%, below the threshold of 4% which had been predetermined as a benchmark for similar outcomes between the two groups. “Therefore, noninferiority of simple hysterectomy to radical hysterectomy could be concluded,” said Dr. Plante.

There were no statistically significant differences in intraoperative complications or mortality between the groups.
 

Surgery-related adverse events greater in radical hysterectomy group

There were some differences between the groups with respect to surgery-related adverse events. Within 4 weeks of surgery, there was a greater incidence of any adverse event in the radical hysterectomy group (50.6% vs. 42.6%; P = .04), as well as greater incidences of urinary incontinence (5.5% vs. 2.4%; P = .048) and urinary retention (11.0% vs. 0.6%; P < .0001). In the 4 weeks following surgery, there was a trend toward more surgery-related adverse events in the radical hysterectomy group (60.5% vs. 53.6%; P = .08) and higher incidences of urinary incontinence (11.0% vs. 4.7%; P = .003) and urinary retention (9.9% vs. 0.6%; P < .0001).

“Urinary incontinence and urinary retention are statistically worse in the radical hysterectomy group – both acutely, as well as [during] the following four weeks after surgery, suggesting that the problem persisted over time,” said Dr. Plante.

Dr. Plante also presented the study at a premeeting virtual press conference, during which Kathleen Moore, MD, provided comments on the study. She expressed enthusiasm about the results.

“Amongst those carefully selected tumors, radical hysterectomy can be converted to a simple hysterectomy, including minimally invasive. You still have to do nodes – that’s an important thing to remember – but you can do this without loss of oncologic control. And importantly, with reduction in surgical complications, postop morbidity, specifically neurologic morbidity. The moment this is presented [at the ASCO conference] this will be the new standard of care, and it represents a huge step forward in the care of women with early-stage cervical cancer,” said Dr. Moore, who is a professor of gynecologic oncology at the University of Oklahoma Health Sciences Center, Oklahoma City.

Also in the press conference, Dr. Plante emphasized the importance of a thorough understanding of the tumor, including size, imaging, and pathology. “The more conservative one wants to be, the more meticulous, the more careful one has to be to make sure that we’re truly dealing with low-risk patients.”

During the question-and-answer session following her presentation at the ASCO session, a moderator asked Dr. Plante if the presence of lymph vascular space invasion (LVSI) should prompt a radical hysterectomy.

Dr. Plante noted that about 13% of both radical and simple hysterectomy groups had LVSI present. “I think the key thing is careful selection, but I’m not sure that we should exclude LVSI [from consideration for simple hysterectomy] de facto,” she said.

Dr. Plante has consulted or advised Merck Serono and has received travel, accommodations, or other expenses from AstraZeneca. Dr. Moore has consulted, advised, and received research funding and travel expenses from numerous pharmaceutical companies.

CHICAGO – When it comes to preventing pelvic recurrence in low-risk cervical cancer, simple hysterectomy is not inferior to radical hysterectomy, according to results from a phase 3, randomized, controlled trial.

“Following adequate and rigorous preoperative assessment, and that’s key – very careful [patient selection] – simple hysterectomies can now be considered the new standard of care for patients with low-risk early-stage cervical cancer,” said Marie Plante, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. A simple hysterectomy removes the uterus and cervix, while a radical hysterectomy also removes the parametrium and upper vagina.

Cervical cancer incidence has gone down over the past 2 decades as a result of improved screening, and patients tend to be lower in age and are more likely to have low-risk, early-stage disease, according to Dr. Plante. “Although radical surgery is highly effective for the treatment of low-risk disease, women are at risk of suffering survivorship issues related to long-term surgical side effects including compromised bladder, bowel, and sexual function,” said Dr. Plante, who is a professor of obstetrics and gynecology at Laval University and head of clinical research at l’Hôtel-Dieu de Québec, both in Quebec City.

Retrospective studies found that infiltration of the parametrium is quite rare in low-risk cases, “suggesting that less radical surgery may be a safe option associated with decreased morbidity – what we call surgical de-escalation,” said Dr. Plante.

To test that idea more rigorously, the researchers designed the SHAPE trial, which randomized 700 women to a simple hysterectomy or radical hysterectomy. Patients were carefully selected to be low risk, having squamous cell, adenocarcinoma, or adenosquamous carcinoma, stage IA2 or IB2 tumors, fewer than 10 mm of stromal invasion on loop electrosurgical excision procedure or cone biopsy, less than 50% stromal invasion seen in MRI, and a maximum tumor dimension of 20 mm or less. Tumors were grade I-III or not assessable.

Over a median follow-up of 4.5 years, pelvic recurrence was 2.52% in the simple hysterectomy group and 2.17% in the radical hysterectomy group. The difference between the recurrence rate between the two groups was 0.35%, with an upper 95% confidence limit of 2.32%, below the threshold of 4% which had been predetermined as a benchmark for similar outcomes between the two groups. “Therefore, noninferiority of simple hysterectomy to radical hysterectomy could be concluded,” said Dr. Plante.

There were no statistically significant differences in intraoperative complications or mortality between the groups.
 

Surgery-related adverse events greater in radical hysterectomy group

There were some differences between the groups with respect to surgery-related adverse events. Within 4 weeks of surgery, there was a greater incidence of any adverse event in the radical hysterectomy group (50.6% vs. 42.6%; P = .04), as well as greater incidences of urinary incontinence (5.5% vs. 2.4%; P = .048) and urinary retention (11.0% vs. 0.6%; P < .0001). In the 4 weeks following surgery, there was a trend toward more surgery-related adverse events in the radical hysterectomy group (60.5% vs. 53.6%; P = .08) and higher incidences of urinary incontinence (11.0% vs. 4.7%; P = .003) and urinary retention (9.9% vs. 0.6%; P < .0001).

“Urinary incontinence and urinary retention are statistically worse in the radical hysterectomy group – both acutely, as well as [during] the following four weeks after surgery, suggesting that the problem persisted over time,” said Dr. Plante.

Dr. Plante also presented the study at a premeeting virtual press conference, during which Kathleen Moore, MD, provided comments on the study. She expressed enthusiasm about the results.

“Amongst those carefully selected tumors, radical hysterectomy can be converted to a simple hysterectomy, including minimally invasive. You still have to do nodes – that’s an important thing to remember – but you can do this without loss of oncologic control. And importantly, with reduction in surgical complications, postop morbidity, specifically neurologic morbidity. The moment this is presented [at the ASCO conference] this will be the new standard of care, and it represents a huge step forward in the care of women with early-stage cervical cancer,” said Dr. Moore, who is a professor of gynecologic oncology at the University of Oklahoma Health Sciences Center, Oklahoma City.

Also in the press conference, Dr. Plante emphasized the importance of a thorough understanding of the tumor, including size, imaging, and pathology. “The more conservative one wants to be, the more meticulous, the more careful one has to be to make sure that we’re truly dealing with low-risk patients.”

During the question-and-answer session following her presentation at the ASCO session, a moderator asked Dr. Plante if the presence of lymph vascular space invasion (LVSI) should prompt a radical hysterectomy.

Dr. Plante noted that about 13% of both radical and simple hysterectomy groups had LVSI present. “I think the key thing is careful selection, but I’m not sure that we should exclude LVSI [from consideration for simple hysterectomy] de facto,” she said.

Dr. Plante has consulted or advised Merck Serono and has received travel, accommodations, or other expenses from AstraZeneca. Dr. Moore has consulted, advised, and received research funding and travel expenses from numerous pharmaceutical companies.

Mailing do-it-yourself sampling kits to test for cervical cancer doubled the rate of screening in a population of low-income and under-screened women, researchers say. 

The self-sampling kits, which detect human papillomavirus (HPV), are available only for use in clinical trials, but the researchers hope that eventually these kits will be approved for use by the general public. 

The researchers, from the University of North Carolina, explored use of these kits in the My Body, My Test-3 study, which was published online in The Lancet Public Health.

In a commentary published with the study, Runzhi Wang, MD, and Jennell Coleman, MD, MPH, both of Johns Hopkins University, Baltimore, said it “provides the required evidence that ... self-collected samples can be an effective strategy for hard-to-reach populations.”

The study involved 665 women (aged 25-64) in North Carolina who were either uninsured or enrolled in Medicaid or Medicare. The patients had low-income backgrounds and lived in urban areas. More than half self-reported as Black or Hispanic (55%), uninsured (78%) or unemployed (57%). None had a Pap smear in at least 4 years or a high-risk HPV test in the last 6 years. 

Two-thirds of the women were mailed an HPV self-collection kit and received assistance with scheduling an in-person screening appointment. The kit included a Viba-Brush device, which is inserted into the vagina like a tampon to collect the sample.

The other third of women, the control group, only received scheduling assistance.

The team found that mailing the self-collection tests along with helping women book in-clinic appointments improved screening rates twofold, compared with just assisting patients to schedule an appointment. 

Screening success among those who received the at-home collection kit was 72%, compared with 37% in the control group. 

Of those who received the kits, 78% returned them. This is “impressive,” said Dr. Wang and Dr. Coleman, as previous studies have reported return rates of only 8%-20%.

University of North Carolina

About 23% of eligible women are overdue for cervical cancer screening by at least a year, according to the National Cancer Institute. Jennifer Smith, PhD, MPH, professor of epidemiology at the University of North Carolina at Chapel Hill and an author of the study, believes every woman deserves equal access to cervical screening.

“I think we really need to make efforts to increase cervical cancer screening among women who are overdue for screening by a year or more from the recommended guidelines,” Dr. Smith said. “We’ve proven along with the wide evidence both in the U.S. and globally that self-collection intervention works well and can motivate screening uptake by breaking down barriers for populations that have less access to care.”

“We’re hoping this research in combination with all of the extensive evidence on the positive performance of HPV self-collection will provide additional information to be considered by the FDA for approval of the kits for primary screening,” Dr. Smith said. 

University of North Carolina

“Government approval of at-home HPV tests would have a huge impact,” said coauthor Noel Brewer, PhD, also of UNC Chapel Hill. “We could better reach those in rural areas where cervical cancer screening is hard to come by.”

Dr. Smith has received research grants, supply donations, and consultancies for Hologic and BD Diagnostics. Dr. Brewer, Dr. Wang, and Dr. Coleman reported no conflicts of interest.

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

Mailing do-it-yourself sampling kits to test for cervical cancer doubled the rate of screening in a population of low-income and under-screened women, researchers say. 

The self-sampling kits, which detect human papillomavirus (HPV), are available only for use in clinical trials, but the researchers hope that eventually these kits will be approved for use by the general public. 

The researchers, from the University of North Carolina, explored use of these kits in the My Body, My Test-3 study, which was published online in The Lancet Public Health.

In a commentary published with the study, Runzhi Wang, MD, and Jennell Coleman, MD, MPH, both of Johns Hopkins University, Baltimore, said it “provides the required evidence that ... self-collected samples can be an effective strategy for hard-to-reach populations.”

The study involved 665 women (aged 25-64) in North Carolina who were either uninsured or enrolled in Medicaid or Medicare. The patients had low-income backgrounds and lived in urban areas. More than half self-reported as Black or Hispanic (55%), uninsured (78%) or unemployed (57%). None had a Pap smear in at least 4 years or a high-risk HPV test in the last 6 years. 

Two-thirds of the women were mailed an HPV self-collection kit and received assistance with scheduling an in-person screening appointment. The kit included a Viba-Brush device, which is inserted into the vagina like a tampon to collect the sample.

The other third of women, the control group, only received scheduling assistance.

The team found that mailing the self-collection tests along with helping women book in-clinic appointments improved screening rates twofold, compared with just assisting patients to schedule an appointment. 

Screening success among those who received the at-home collection kit was 72%, compared with 37% in the control group. 

Of those who received the kits, 78% returned them. This is “impressive,” said Dr. Wang and Dr. Coleman, as previous studies have reported return rates of only 8%-20%.

University of North Carolina

About 23% of eligible women are overdue for cervical cancer screening by at least a year, according to the National Cancer Institute. Jennifer Smith, PhD, MPH, professor of epidemiology at the University of North Carolina at Chapel Hill and an author of the study, believes every woman deserves equal access to cervical screening.

“I think we really need to make efforts to increase cervical cancer screening among women who are overdue for screening by a year or more from the recommended guidelines,” Dr. Smith said. “We’ve proven along with the wide evidence both in the U.S. and globally that self-collection intervention works well and can motivate screening uptake by breaking down barriers for populations that have less access to care.”

“We’re hoping this research in combination with all of the extensive evidence on the positive performance of HPV self-collection will provide additional information to be considered by the FDA for approval of the kits for primary screening,” Dr. Smith said. 

University of North Carolina

“Government approval of at-home HPV tests would have a huge impact,” said coauthor Noel Brewer, PhD, also of UNC Chapel Hill. “We could better reach those in rural areas where cervical cancer screening is hard to come by.”

Dr. Smith has received research grants, supply donations, and consultancies for Hologic and BD Diagnostics. Dr. Brewer, Dr. Wang, and Dr. Coleman reported no conflicts of interest.

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

Mailing do-it-yourself sampling kits to test for cervical cancer doubled the rate of screening in a population of low-income and under-screened women, researchers say. 

The self-sampling kits, which detect human papillomavirus (HPV), are available only for use in clinical trials, but the researchers hope that eventually these kits will be approved for use by the general public. 

The researchers, from the University of North Carolina, explored use of these kits in the My Body, My Test-3 study, which was published online in The Lancet Public Health.

In a commentary published with the study, Runzhi Wang, MD, and Jennell Coleman, MD, MPH, both of Johns Hopkins University, Baltimore, said it “provides the required evidence that ... self-collected samples can be an effective strategy for hard-to-reach populations.”

The study involved 665 women (aged 25-64) in North Carolina who were either uninsured or enrolled in Medicaid or Medicare. The patients had low-income backgrounds and lived in urban areas. More than half self-reported as Black or Hispanic (55%), uninsured (78%) or unemployed (57%). None had a Pap smear in at least 4 years or a high-risk HPV test in the last 6 years. 

Two-thirds of the women were mailed an HPV self-collection kit and received assistance with scheduling an in-person screening appointment. The kit included a Viba-Brush device, which is inserted into the vagina like a tampon to collect the sample.

The other third of women, the control group, only received scheduling assistance.

The team found that mailing the self-collection tests along with helping women book in-clinic appointments improved screening rates twofold, compared with just assisting patients to schedule an appointment. 

Screening success among those who received the at-home collection kit was 72%, compared with 37% in the control group. 

Of those who received the kits, 78% returned them. This is “impressive,” said Dr. Wang and Dr. Coleman, as previous studies have reported return rates of only 8%-20%.

University of North Carolina

About 23% of eligible women are overdue for cervical cancer screening by at least a year, according to the National Cancer Institute. Jennifer Smith, PhD, MPH, professor of epidemiology at the University of North Carolina at Chapel Hill and an author of the study, believes every woman deserves equal access to cervical screening.

“I think we really need to make efforts to increase cervical cancer screening among women who are overdue for screening by a year or more from the recommended guidelines,” Dr. Smith said. “We’ve proven along with the wide evidence both in the U.S. and globally that self-collection intervention works well and can motivate screening uptake by breaking down barriers for populations that have less access to care.”

“We’re hoping this research in combination with all of the extensive evidence on the positive performance of HPV self-collection will provide additional information to be considered by the FDA for approval of the kits for primary screening,” Dr. Smith said. 

University of North Carolina

“Government approval of at-home HPV tests would have a huge impact,” said coauthor Noel Brewer, PhD, also of UNC Chapel Hill. “We could better reach those in rural areas where cervical cancer screening is hard to come by.”

Dr. Smith has received research grants, supply donations, and consultancies for Hologic and BD Diagnostics. Dr. Brewer, Dr. Wang, and Dr. Coleman reported no conflicts of interest.

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