AVAHO

Across patients’ age groups, adding the immune checkpoint inhibitor nivolumab to chemotherapy significantly improves progression-free survival in advanced stage Hodgkin lymphoma while also reducing toxicities, making it a new standard of care, compared with the CD30-targeting drug brentuximab vedotin.

“[SWOG] S1826, the largest Hodgkin lymphoma study in National Clinical Trials Network history, is a key step toward harmonizing the pediatric and adult treatment of advanced-stage Hodgkin lymphoma,” the authors reported in late-breaking research presented at the annual meeting of the American Society of Clinical Oncology.

“Based on the magnitude of the benefit and with nivolumab being better tolerated than brentuximab, we anticipate that these results will be practice changing and nivolumab [and chemotherapy] will become a new standard of care,” lead author Alex Francisco Herrera, MD, an associate professor and chief of the division of lymphoma in the department of hematology and hematopoietic cell transplantation, City of Hope Medical Center, Duarte, Calif., said in an interview.

The randomized SWOG S1826 trial of 976 patients with newly diagnosed stage 3 or 4 Hodgkin lymphoma included patients ranging in age from as young as 12 to 83 years, and at a median follow-up of 12.1 months, the addition of nivolumab to the chemotherapy regimen of doxorubicin, vinblastine, and dacarbazine (AVD) was associated with as much as a 52% reduction in the risk of disease-related death, compared with the addition of brentuximab.

The results are especially important considering that Hodgkin lymphoma disproportionately affects younger patients, including those in their teens, 20s, and 30s, Dr. Herrera noted in an interview.

“We found that treatment with nivolumab reduced the risk of progression by half, and, importantly, the benefit was observed across subgroups,” he said.
 

Relapse/refractory disease common in advanced HL

In general, outcomes are relatively good even for stage III or IV Hodgkin lymphoma; however, about a quarter of patients still have relapses or refractory disease.

While the introduction of novel frontline treatment with brentuximab-AVD was important in improving overall survival, the regimen adds toxicity, particularly among older patients, and many pediatric patients receiving the therapy still require radiation therapy, with its undesirable side effects.

Meanwhile, the progressive death 1 inhibitor nivolumab, approved by the Food and Drug Administration, gained interest as a potentially ideal alternative in light of Hodgkin lymphoma’s status basically as “the poster child for PD-1 blockade,” Dr. Herrera said.

“There are genetic changes in the Hodgkin lymphoma tumor cell that lead to expression of PD-1 ligands on the surface of Hodgkin lymphoma cells, and when we use a drug like nivolumab, we see that even patients with the most treatment-resistant rates of lymphoma have as much as a 70% response rate,” he explained in a press briefing.

To further investigate, the first-of-its-kind collaboration of adult and pediatric cancer teams conducted the S1826 trial to evaluate the treatment across age groups with stage 3 and 4 Hodgkin lymphoma.

For the study, conducted between July 2019 and October 2022, 976 patients were randomized to treatment either with nivolumab (n = 489) or brentuximab (n = 487), each in combination with the AVD regimen.

Of the patients, the median age was 27, with 24% under the age of 18, 10% over 60 and 32% with IPS 4-7. Among them, 56% were male and 76% were White.

For the primary endpoint, at a median follow-up of 12.1 months, the rate of progression-free survival was significantly higher in the nivolumab arm (hazard ratio, 0.48; one-sided P = .0005), with the rate of 1-year survival at 94% in the nivolumab group versus 86% in the brentuximab group, for a 52% reduction in the risk of disease-related death with nivolumab versus brentuximab.

A total of 11 deaths occurred in the brentuximab group, 7 of which were related to adverse events, compared with 4 deaths in the nivolumab group, 3 of which were related to nivolumab.

Importantly, fewer than 1% of patients with nivolumab required radiation therapy.

“That’s a dramatic reduction of the proportion of the very youngest patients receiving radiotherapy,” Dr. Herrera noted.

Grade 3 or higher hematologic adverse events were higher in the nivolumab group, at 48.4%, including 45.1% that were grade 3 or higher neutropenia, compared with 30.5% with brentuximab, including 23.9% with grade 3 or higher neutropenia.

However, rates of any grade of febrile neutropenia were similar with nivolumab and brentuximab (5.6% vs. 6.4%, respectively), as were rates of pneumonitis (2.0% vs. 3.2%), ALT elevation (30.7% vs. 39.8%), and colitis (1% vs. 1.3%).

In addition, rates of hypo- and hyperthyroidism were more frequent after nivolumab (7% and 3% with nivolumab, respectively, vs. fewer than 1% with brentuximab).

But, of note, peripheral neuropathy of any grade was more common after brentuximab (sensory: 28.1% nivolumab vs. 54.2% brentuximab; motor: 4% nivolumab vs. 6.8% brentuximab).

“I can’t emphasize how important neuropathy is as a side effect in these young patients who have the rest of their life ahead of them,” Dr. Herrera explained. “It’s fantastic to be cured of cancer, but tough to not be able to feel your fingers and toes.”

With its broad inclusion of age groups and a diverse population, he added that the study was importantly a “representative” trial, reflecting a “real-world population.”

“Incredibly, a quarter of patients were under the age of 18; 10% were over the age of 60, a quarter of patients were Hispanic and Black, and in fact we had a quite good representation of higher-risk subgroups,” he said.

Looking forward, longer-term follow-up from this study will be important in determining if the improvement observed in disease-related deaths is maintained over time, Dr. Herrera noted.

“Additionally, it is crucial to obtain data on other key outcomes such as overall survival and quality of life from longer-term follow of this study,” he said.
 

‘A huge step forward’

Commenting on the study, Oreofe Odejide, MD, a medical oncologist at the Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, both in Boston, said that results were unprecedented.

“Although a majority of patients with advanced stage Hodgkin lymphoma will be cured with initial therapy, about 20% of patients still end up with relapsed or refractory disease,” she said in an interview. “Therefore, the findings from this study represent a huge step forward in the management of advanced Hodgkin lymphoma in children and adults, leading to an improved and well-tolerated standard of care.”

Dr. Odejide agreed that the findings are potentially practice changing.

“Brentuximab-AVD set a high bar for the treatment of advanced-stage Hodgkin lymphoma, as it was the first regimen to show a meaningful improvement in disease-related death compared to ABVD chemotherapy in several years,” she explained.

“The fact that the SWOG1826 trial now shows a significant benefit of nivolumab-AVD over brentuximab and included both pediatric and adult patients unlike prior studies, is highly compelling,” Dr. Odejide added. “This has strong potential to change the standard of care for patients with previously untreated, advanced-stage Hodgkin lymphoma.”

The study received funding from the National Cancer Institute and from Bristol-Myers Squibb. Dr. Herrera reported relationships with Abbvie, ADC Therapeutics, Adicet Bio, AstraZeneca/MedImmune, Bristol-Myers Squibb, Caribou Biosciences, Genentech/Roche, Genmab, Karyopharm Therapeutics, Merck, Pfizer, Regeneron, Seagen, Takeda, and Tubulis Gmbh. Dr. Odejide reported no disclosures.

Across patients’ age groups, adding the immune checkpoint inhibitor nivolumab to chemotherapy significantly improves progression-free survival in advanced stage Hodgkin lymphoma while also reducing toxicities, making it a new standard of care, compared with the CD30-targeting drug brentuximab vedotin.

“[SWOG] S1826, the largest Hodgkin lymphoma study in National Clinical Trials Network history, is a key step toward harmonizing the pediatric and adult treatment of advanced-stage Hodgkin lymphoma,” the authors reported in late-breaking research presented at the annual meeting of the American Society of Clinical Oncology.

“Based on the magnitude of the benefit and with nivolumab being better tolerated than brentuximab, we anticipate that these results will be practice changing and nivolumab [and chemotherapy] will become a new standard of care,” lead author Alex Francisco Herrera, MD, an associate professor and chief of the division of lymphoma in the department of hematology and hematopoietic cell transplantation, City of Hope Medical Center, Duarte, Calif., said in an interview.

The randomized SWOG S1826 trial of 976 patients with newly diagnosed stage 3 or 4 Hodgkin lymphoma included patients ranging in age from as young as 12 to 83 years, and at a median follow-up of 12.1 months, the addition of nivolumab to the chemotherapy regimen of doxorubicin, vinblastine, and dacarbazine (AVD) was associated with as much as a 52% reduction in the risk of disease-related death, compared with the addition of brentuximab.

The results are especially important considering that Hodgkin lymphoma disproportionately affects younger patients, including those in their teens, 20s, and 30s, Dr. Herrera noted in an interview.

“We found that treatment with nivolumab reduced the risk of progression by half, and, importantly, the benefit was observed across subgroups,” he said.
 

Relapse/refractory disease common in advanced HL

In general, outcomes are relatively good even for stage III or IV Hodgkin lymphoma; however, about a quarter of patients still have relapses or refractory disease.

While the introduction of novel frontline treatment with brentuximab-AVD was important in improving overall survival, the regimen adds toxicity, particularly among older patients, and many pediatric patients receiving the therapy still require radiation therapy, with its undesirable side effects.

Meanwhile, the progressive death 1 inhibitor nivolumab, approved by the Food and Drug Administration, gained interest as a potentially ideal alternative in light of Hodgkin lymphoma’s status basically as “the poster child for PD-1 blockade,” Dr. Herrera said.

“There are genetic changes in the Hodgkin lymphoma tumor cell that lead to expression of PD-1 ligands on the surface of Hodgkin lymphoma cells, and when we use a drug like nivolumab, we see that even patients with the most treatment-resistant rates of lymphoma have as much as a 70% response rate,” he explained in a press briefing.

To further investigate, the first-of-its-kind collaboration of adult and pediatric cancer teams conducted the S1826 trial to evaluate the treatment across age groups with stage 3 and 4 Hodgkin lymphoma.

For the study, conducted between July 2019 and October 2022, 976 patients were randomized to treatment either with nivolumab (n = 489) or brentuximab (n = 487), each in combination with the AVD regimen.

Of the patients, the median age was 27, with 24% under the age of 18, 10% over 60 and 32% with IPS 4-7. Among them, 56% were male and 76% were White.

For the primary endpoint, at a median follow-up of 12.1 months, the rate of progression-free survival was significantly higher in the nivolumab arm (hazard ratio, 0.48; one-sided P = .0005), with the rate of 1-year survival at 94% in the nivolumab group versus 86% in the brentuximab group, for a 52% reduction in the risk of disease-related death with nivolumab versus brentuximab.

A total of 11 deaths occurred in the brentuximab group, 7 of which were related to adverse events, compared with 4 deaths in the nivolumab group, 3 of which were related to nivolumab.

Importantly, fewer than 1% of patients with nivolumab required radiation therapy.

“That’s a dramatic reduction of the proportion of the very youngest patients receiving radiotherapy,” Dr. Herrera noted.

Grade 3 or higher hematologic adverse events were higher in the nivolumab group, at 48.4%, including 45.1% that were grade 3 or higher neutropenia, compared with 30.5% with brentuximab, including 23.9% with grade 3 or higher neutropenia.

However, rates of any grade of febrile neutropenia were similar with nivolumab and brentuximab (5.6% vs. 6.4%, respectively), as were rates of pneumonitis (2.0% vs. 3.2%), ALT elevation (30.7% vs. 39.8%), and colitis (1% vs. 1.3%).

In addition, rates of hypo- and hyperthyroidism were more frequent after nivolumab (7% and 3% with nivolumab, respectively, vs. fewer than 1% with brentuximab).

But, of note, peripheral neuropathy of any grade was more common after brentuximab (sensory: 28.1% nivolumab vs. 54.2% brentuximab; motor: 4% nivolumab vs. 6.8% brentuximab).

“I can’t emphasize how important neuropathy is as a side effect in these young patients who have the rest of their life ahead of them,” Dr. Herrera explained. “It’s fantastic to be cured of cancer, but tough to not be able to feel your fingers and toes.”

With its broad inclusion of age groups and a diverse population, he added that the study was importantly a “representative” trial, reflecting a “real-world population.”

“Incredibly, a quarter of patients were under the age of 18; 10% were over the age of 60, a quarter of patients were Hispanic and Black, and in fact we had a quite good representation of higher-risk subgroups,” he said.

Looking forward, longer-term follow-up from this study will be important in determining if the improvement observed in disease-related deaths is maintained over time, Dr. Herrera noted.

“Additionally, it is crucial to obtain data on other key outcomes such as overall survival and quality of life from longer-term follow of this study,” he said.
 

‘A huge step forward’

Commenting on the study, Oreofe Odejide, MD, a medical oncologist at the Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, both in Boston, said that results were unprecedented.

“Although a majority of patients with advanced stage Hodgkin lymphoma will be cured with initial therapy, about 20% of patients still end up with relapsed or refractory disease,” she said in an interview. “Therefore, the findings from this study represent a huge step forward in the management of advanced Hodgkin lymphoma in children and adults, leading to an improved and well-tolerated standard of care.”

Dr. Odejide agreed that the findings are potentially practice changing.

“Brentuximab-AVD set a high bar for the treatment of advanced-stage Hodgkin lymphoma, as it was the first regimen to show a meaningful improvement in disease-related death compared to ABVD chemotherapy in several years,” she explained.

“The fact that the SWOG1826 trial now shows a significant benefit of nivolumab-AVD over brentuximab and included both pediatric and adult patients unlike prior studies, is highly compelling,” Dr. Odejide added. “This has strong potential to change the standard of care for patients with previously untreated, advanced-stage Hodgkin lymphoma.”

The study received funding from the National Cancer Institute and from Bristol-Myers Squibb. Dr. Herrera reported relationships with Abbvie, ADC Therapeutics, Adicet Bio, AstraZeneca/MedImmune, Bristol-Myers Squibb, Caribou Biosciences, Genentech/Roche, Genmab, Karyopharm Therapeutics, Merck, Pfizer, Regeneron, Seagen, Takeda, and Tubulis Gmbh. Dr. Odejide reported no disclosures.

Across patients’ age groups, adding the immune checkpoint inhibitor nivolumab to chemotherapy significantly improves progression-free survival in advanced stage Hodgkin lymphoma while also reducing toxicities, making it a new standard of care, compared with the CD30-targeting drug brentuximab vedotin.

“[SWOG] S1826, the largest Hodgkin lymphoma study in National Clinical Trials Network history, is a key step toward harmonizing the pediatric and adult treatment of advanced-stage Hodgkin lymphoma,” the authors reported in late-breaking research presented at the annual meeting of the American Society of Clinical Oncology.

“Based on the magnitude of the benefit and with nivolumab being better tolerated than brentuximab, we anticipate that these results will be practice changing and nivolumab [and chemotherapy] will become a new standard of care,” lead author Alex Francisco Herrera, MD, an associate professor and chief of the division of lymphoma in the department of hematology and hematopoietic cell transplantation, City of Hope Medical Center, Duarte, Calif., said in an interview.

The randomized SWOG S1826 trial of 976 patients with newly diagnosed stage 3 or 4 Hodgkin lymphoma included patients ranging in age from as young as 12 to 83 years, and at a median follow-up of 12.1 months, the addition of nivolumab to the chemotherapy regimen of doxorubicin, vinblastine, and dacarbazine (AVD) was associated with as much as a 52% reduction in the risk of disease-related death, compared with the addition of brentuximab.

The results are especially important considering that Hodgkin lymphoma disproportionately affects younger patients, including those in their teens, 20s, and 30s, Dr. Herrera noted in an interview.

“We found that treatment with nivolumab reduced the risk of progression by half, and, importantly, the benefit was observed across subgroups,” he said.
 

Relapse/refractory disease common in advanced HL

In general, outcomes are relatively good even for stage III or IV Hodgkin lymphoma; however, about a quarter of patients still have relapses or refractory disease.

While the introduction of novel frontline treatment with brentuximab-AVD was important in improving overall survival, the regimen adds toxicity, particularly among older patients, and many pediatric patients receiving the therapy still require radiation therapy, with its undesirable side effects.

Meanwhile, the progressive death 1 inhibitor nivolumab, approved by the Food and Drug Administration, gained interest as a potentially ideal alternative in light of Hodgkin lymphoma’s status basically as “the poster child for PD-1 blockade,” Dr. Herrera said.

“There are genetic changes in the Hodgkin lymphoma tumor cell that lead to expression of PD-1 ligands on the surface of Hodgkin lymphoma cells, and when we use a drug like nivolumab, we see that even patients with the most treatment-resistant rates of lymphoma have as much as a 70% response rate,” he explained in a press briefing.

To further investigate, the first-of-its-kind collaboration of adult and pediatric cancer teams conducted the S1826 trial to evaluate the treatment across age groups with stage 3 and 4 Hodgkin lymphoma.

For the study, conducted between July 2019 and October 2022, 976 patients were randomized to treatment either with nivolumab (n = 489) or brentuximab (n = 487), each in combination with the AVD regimen.

Of the patients, the median age was 27, with 24% under the age of 18, 10% over 60 and 32% with IPS 4-7. Among them, 56% were male and 76% were White.

For the primary endpoint, at a median follow-up of 12.1 months, the rate of progression-free survival was significantly higher in the nivolumab arm (hazard ratio, 0.48; one-sided P = .0005), with the rate of 1-year survival at 94% in the nivolumab group versus 86% in the brentuximab group, for a 52% reduction in the risk of disease-related death with nivolumab versus brentuximab.

A total of 11 deaths occurred in the brentuximab group, 7 of which were related to adverse events, compared with 4 deaths in the nivolumab group, 3 of which were related to nivolumab.

Importantly, fewer than 1% of patients with nivolumab required radiation therapy.

“That’s a dramatic reduction of the proportion of the very youngest patients receiving radiotherapy,” Dr. Herrera noted.

Grade 3 or higher hematologic adverse events were higher in the nivolumab group, at 48.4%, including 45.1% that were grade 3 or higher neutropenia, compared with 30.5% with brentuximab, including 23.9% with grade 3 or higher neutropenia.

However, rates of any grade of febrile neutropenia were similar with nivolumab and brentuximab (5.6% vs. 6.4%, respectively), as were rates of pneumonitis (2.0% vs. 3.2%), ALT elevation (30.7% vs. 39.8%), and colitis (1% vs. 1.3%).

In addition, rates of hypo- and hyperthyroidism were more frequent after nivolumab (7% and 3% with nivolumab, respectively, vs. fewer than 1% with brentuximab).

But, of note, peripheral neuropathy of any grade was more common after brentuximab (sensory: 28.1% nivolumab vs. 54.2% brentuximab; motor: 4% nivolumab vs. 6.8% brentuximab).

“I can’t emphasize how important neuropathy is as a side effect in these young patients who have the rest of their life ahead of them,” Dr. Herrera explained. “It’s fantastic to be cured of cancer, but tough to not be able to feel your fingers and toes.”

With its broad inclusion of age groups and a diverse population, he added that the study was importantly a “representative” trial, reflecting a “real-world population.”

“Incredibly, a quarter of patients were under the age of 18; 10% were over the age of 60, a quarter of patients were Hispanic and Black, and in fact we had a quite good representation of higher-risk subgroups,” he said.

Looking forward, longer-term follow-up from this study will be important in determining if the improvement observed in disease-related deaths is maintained over time, Dr. Herrera noted.

“Additionally, it is crucial to obtain data on other key outcomes such as overall survival and quality of life from longer-term follow of this study,” he said.
 

‘A huge step forward’

Commenting on the study, Oreofe Odejide, MD, a medical oncologist at the Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, both in Boston, said that results were unprecedented.

“Although a majority of patients with advanced stage Hodgkin lymphoma will be cured with initial therapy, about 20% of patients still end up with relapsed or refractory disease,” she said in an interview. “Therefore, the findings from this study represent a huge step forward in the management of advanced Hodgkin lymphoma in children and adults, leading to an improved and well-tolerated standard of care.”

Dr. Odejide agreed that the findings are potentially practice changing.

“Brentuximab-AVD set a high bar for the treatment of advanced-stage Hodgkin lymphoma, as it was the first regimen to show a meaningful improvement in disease-related death compared to ABVD chemotherapy in several years,” she explained.

“The fact that the SWOG1826 trial now shows a significant benefit of nivolumab-AVD over brentuximab and included both pediatric and adult patients unlike prior studies, is highly compelling,” Dr. Odejide added. “This has strong potential to change the standard of care for patients with previously untreated, advanced-stage Hodgkin lymphoma.”

The study received funding from the National Cancer Institute and from Bristol-Myers Squibb. Dr. Herrera reported relationships with Abbvie, ADC Therapeutics, Adicet Bio, AstraZeneca/MedImmune, Bristol-Myers Squibb, Caribou Biosciences, Genentech/Roche, Genmab, Karyopharm Therapeutics, Merck, Pfizer, Regeneron, Seagen, Takeda, and Tubulis Gmbh. Dr. Odejide reported no disclosures.

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Patients with resectable, early-stage pancreatic cancer can safely undergo minimally invasive distal pancreatectomy (MIDP) as an alternative to traditional open surgery, suggest results from the international DIPLOMA study.

In the trial, around 260 patients were randomly assigned to undergo either open surgery or minimally invasive laparoscopic or robot-assisted surgery. Rates of complete tumor removal were comparable between the groups.

In addition, the disease-free and overall survival rates at 3 years were nearly identical.

“For pancreatic cancer, we have proven for the first time that minimally invasive distal pancreatectomy is as good as open surgery,” commented principal investigator Mohammad Abu Hilal, MD, PhD, surgical director at the Instituto Ospedaliero Fondazione Poliambulanza in Brescia, Italy.

“Our research provides reassurance for surgeons and can help patients by giving them the information they need to have a conversation with their doctor about how they want to be treated,” he added.

Dr. Hilal was speaking at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented (abstract 4163) on June 5.

The study was not able to show that there was a benefit in terms of shorter hospital stays or greater functional recovery with the minimally invasive approach, Dr. Hilal noted, but he suggested that this could be because of differences in postoperative procedures between the participating centers.

He said in an interview that minimally invasive surgery is becoming “very common all over the world,” particularly in the United States, and that randomized controlled trials are “always the last step” in convincing people to use the technique.

He also emphasized that the “best results are obtained in high-volume centers where surgeons do more than at least 50 pancreatic resections a year,” because the minimally invasive approach is “quite complex and difficult,” more so than open surgery.

“This confirmatory study proves that minimally invasive surgical techniques are a safe and effective option for resectable pancreatic cancer,” commented ASCO expert Jennifer F. Tseng, MD, chair of surgery at Boston University and surgeon-in-chief at the Boston Medical Center. It may also “provide benefits like faster recovery time and less infection risk, without increasing cancer risk.”

The results from this trial “will help both surgeons and patients feel comfortable that minimally invasive surgery, in expert hands, is not inferior to open surgery,” she commented in a statement.
 

Minimally invasive surgery

Only around 12% of patients with pancreatic cancer are diagnosed when the disease is at an early enough stage for surgical resection to be a possibility, Dr. Hilal noted. Minimally invasive pancreatectomy, particularly the distal procedure, was introduced around 25 years ago, but it was initially used only for benign tumors or borderline malignancies.

It took another 10 years before it was considered in cases of confirmed malignancies, “and the main reason for this delay was concerns about the oncological efficiency” of MIDP in terms of its ability to achieve radical resection and an adequate lymph node yield. At the same time, some concerns about minimally invasive surgery for cancer were raised because of results from randomized trials in other cancer types, such as hysterectomy for cervical cancer. Some studies showed worse survival after minimally invasive surgery than after open surgery.

In recent years, use of minimally invasive techniques for pancreatic cancer has become an increasingly “hot topic in many surgical forums,” Dr. Hilal said.

So his team set out to investigate the approach in a phase 3 noninferiority trial. The investigators focused on patients who had an indication for elective distal pancreatectomy plus splenectomy because of proven or highly suspected pancreatic ductal adenocarcinoma in the pancreatic body or tail.

Patients from 35 centers in 12 countries were recruited between May 2018 and May 2021 and were randomly assigned to undergo either MIDP or open distal pancreatectomy.

Patients, nurses, and pathologists were blinded to the surgical procedure by covering of the abdominal wall.

None of the patients underwent adjuvant or neoadjuvant chemotherapy.

Following the procedure, the patients were followed up at 2 weeks and at 1, 3, 6, and 12 months, and a CT scan was performed at 12 months. A range of assessments was performed at each visit, including quality of life measures.

From 1,146 patients initially screened, 261 patients were included.

A few patients withdrew; 131 patients underwent MIDP, and 127 underwent open surgery and were included in the intention-to-treat analysis. Of those, 129 and 125, respectively, were included in the follow-up analysis.

The results confirmed the noninferiority of MIDP, compared with open surgery, with a rate of R0 radical resection (defined as ≥ 1 mm distance between the tumor and the surgical margin) of 73% vs. 69% (P = .039).

In addition, the lymph node yield was comparable between the two approaches, at an average of 22 nodes for MIDP vs. 23 for open surgery (P = .89), and the time to functional recovery was identical, at 5 days for both (P = .22).

The rate of intraperitoneal recurrence was found to be 41% with MIDP, compared with 38% for patients who underwent open surgery.

Dr. Hilal also showed that the rate of serious adverse events, such as bleeding or organ damage, was similar between the two procedures, at 18% with minimally invasive surgery vs. 22% for the open procedure.

Turning to the survival curves, he noted that it is “very clear” that the two procedures achieved near-identical results, at a hazard ratio of 0.99 (P = .94) for overall survival and 0.97 (P = .88) for disease-free survival when comparing MIDP with open surgery.

The researchers will continue to follow up the patients for 3-5 years and will analyze the lymph nodes retrieved to determine whether removal of the spleen is necessary.

The study was funded by Medtronic and Ethicon. Dr. Hilal has relationships with Ethicon and Medtronic. Dr. Tseng has relationships with Aegerion, Amgen, AstraZeneca, Bristol-Myers Squibb, Cubist, Curadel Surgical Innovations, Daiichi Sankyo/Lilly, GlaxoSmithKline, Intarcia Therapeutics, Merck, MyoKardia, PanTher Therapeutics, Pfizer, Quest Diagnostics, Sanofi, Vertex, and Zeus.

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

Patients with resectable, early-stage pancreatic cancer can safely undergo minimally invasive distal pancreatectomy (MIDP) as an alternative to traditional open surgery, suggest results from the international DIPLOMA study.

In the trial, around 260 patients were randomly assigned to undergo either open surgery or minimally invasive laparoscopic or robot-assisted surgery. Rates of complete tumor removal were comparable between the groups.

In addition, the disease-free and overall survival rates at 3 years were nearly identical.

“For pancreatic cancer, we have proven for the first time that minimally invasive distal pancreatectomy is as good as open surgery,” commented principal investigator Mohammad Abu Hilal, MD, PhD, surgical director at the Instituto Ospedaliero Fondazione Poliambulanza in Brescia, Italy.

“Our research provides reassurance for surgeons and can help patients by giving them the information they need to have a conversation with their doctor about how they want to be treated,” he added.

Dr. Hilal was speaking at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented (abstract 4163) on June 5.

The study was not able to show that there was a benefit in terms of shorter hospital stays or greater functional recovery with the minimally invasive approach, Dr. Hilal noted, but he suggested that this could be because of differences in postoperative procedures between the participating centers.

He said in an interview that minimally invasive surgery is becoming “very common all over the world,” particularly in the United States, and that randomized controlled trials are “always the last step” in convincing people to use the technique.

He also emphasized that the “best results are obtained in high-volume centers where surgeons do more than at least 50 pancreatic resections a year,” because the minimally invasive approach is “quite complex and difficult,” more so than open surgery.

“This confirmatory study proves that minimally invasive surgical techniques are a safe and effective option for resectable pancreatic cancer,” commented ASCO expert Jennifer F. Tseng, MD, chair of surgery at Boston University and surgeon-in-chief at the Boston Medical Center. It may also “provide benefits like faster recovery time and less infection risk, without increasing cancer risk.”

The results from this trial “will help both surgeons and patients feel comfortable that minimally invasive surgery, in expert hands, is not inferior to open surgery,” she commented in a statement.
 

Minimally invasive surgery

Only around 12% of patients with pancreatic cancer are diagnosed when the disease is at an early enough stage for surgical resection to be a possibility, Dr. Hilal noted. Minimally invasive pancreatectomy, particularly the distal procedure, was introduced around 25 years ago, but it was initially used only for benign tumors or borderline malignancies.

It took another 10 years before it was considered in cases of confirmed malignancies, “and the main reason for this delay was concerns about the oncological efficiency” of MIDP in terms of its ability to achieve radical resection and an adequate lymph node yield. At the same time, some concerns about minimally invasive surgery for cancer were raised because of results from randomized trials in other cancer types, such as hysterectomy for cervical cancer. Some studies showed worse survival after minimally invasive surgery than after open surgery.

In recent years, use of minimally invasive techniques for pancreatic cancer has become an increasingly “hot topic in many surgical forums,” Dr. Hilal said.

So his team set out to investigate the approach in a phase 3 noninferiority trial. The investigators focused on patients who had an indication for elective distal pancreatectomy plus splenectomy because of proven or highly suspected pancreatic ductal adenocarcinoma in the pancreatic body or tail.

Patients from 35 centers in 12 countries were recruited between May 2018 and May 2021 and were randomly assigned to undergo either MIDP or open distal pancreatectomy.

Patients, nurses, and pathologists were blinded to the surgical procedure by covering of the abdominal wall.

None of the patients underwent adjuvant or neoadjuvant chemotherapy.

Following the procedure, the patients were followed up at 2 weeks and at 1, 3, 6, and 12 months, and a CT scan was performed at 12 months. A range of assessments was performed at each visit, including quality of life measures.

From 1,146 patients initially screened, 261 patients were included.

A few patients withdrew; 131 patients underwent MIDP, and 127 underwent open surgery and were included in the intention-to-treat analysis. Of those, 129 and 125, respectively, were included in the follow-up analysis.

The results confirmed the noninferiority of MIDP, compared with open surgery, with a rate of R0 radical resection (defined as ≥ 1 mm distance between the tumor and the surgical margin) of 73% vs. 69% (P = .039).

In addition, the lymph node yield was comparable between the two approaches, at an average of 22 nodes for MIDP vs. 23 for open surgery (P = .89), and the time to functional recovery was identical, at 5 days for both (P = .22).

The rate of intraperitoneal recurrence was found to be 41% with MIDP, compared with 38% for patients who underwent open surgery.

Dr. Hilal also showed that the rate of serious adverse events, such as bleeding or organ damage, was similar between the two procedures, at 18% with minimally invasive surgery vs. 22% for the open procedure.

Turning to the survival curves, he noted that it is “very clear” that the two procedures achieved near-identical results, at a hazard ratio of 0.99 (P = .94) for overall survival and 0.97 (P = .88) for disease-free survival when comparing MIDP with open surgery.

The researchers will continue to follow up the patients for 3-5 years and will analyze the lymph nodes retrieved to determine whether removal of the spleen is necessary.

The study was funded by Medtronic and Ethicon. Dr. Hilal has relationships with Ethicon and Medtronic. Dr. Tseng has relationships with Aegerion, Amgen, AstraZeneca, Bristol-Myers Squibb, Cubist, Curadel Surgical Innovations, Daiichi Sankyo/Lilly, GlaxoSmithKline, Intarcia Therapeutics, Merck, MyoKardia, PanTher Therapeutics, Pfizer, Quest Diagnostics, Sanofi, Vertex, and Zeus.

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

Patients with resectable, early-stage pancreatic cancer can safely undergo minimally invasive distal pancreatectomy (MIDP) as an alternative to traditional open surgery, suggest results from the international DIPLOMA study.

In the trial, around 260 patients were randomly assigned to undergo either open surgery or minimally invasive laparoscopic or robot-assisted surgery. Rates of complete tumor removal were comparable between the groups.

In addition, the disease-free and overall survival rates at 3 years were nearly identical.

“For pancreatic cancer, we have proven for the first time that minimally invasive distal pancreatectomy is as good as open surgery,” commented principal investigator Mohammad Abu Hilal, MD, PhD, surgical director at the Instituto Ospedaliero Fondazione Poliambulanza in Brescia, Italy.

“Our research provides reassurance for surgeons and can help patients by giving them the information they need to have a conversation with their doctor about how they want to be treated,” he added.

Dr. Hilal was speaking at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented (abstract 4163) on June 5.

The study was not able to show that there was a benefit in terms of shorter hospital stays or greater functional recovery with the minimally invasive approach, Dr. Hilal noted, but he suggested that this could be because of differences in postoperative procedures between the participating centers.

He said in an interview that minimally invasive surgery is becoming “very common all over the world,” particularly in the United States, and that randomized controlled trials are “always the last step” in convincing people to use the technique.

He also emphasized that the “best results are obtained in high-volume centers where surgeons do more than at least 50 pancreatic resections a year,” because the minimally invasive approach is “quite complex and difficult,” more so than open surgery.

“This confirmatory study proves that minimally invasive surgical techniques are a safe and effective option for resectable pancreatic cancer,” commented ASCO expert Jennifer F. Tseng, MD, chair of surgery at Boston University and surgeon-in-chief at the Boston Medical Center. It may also “provide benefits like faster recovery time and less infection risk, without increasing cancer risk.”

The results from this trial “will help both surgeons and patients feel comfortable that minimally invasive surgery, in expert hands, is not inferior to open surgery,” she commented in a statement.
 

Minimally invasive surgery

Only around 12% of patients with pancreatic cancer are diagnosed when the disease is at an early enough stage for surgical resection to be a possibility, Dr. Hilal noted. Minimally invasive pancreatectomy, particularly the distal procedure, was introduced around 25 years ago, but it was initially used only for benign tumors or borderline malignancies.

It took another 10 years before it was considered in cases of confirmed malignancies, “and the main reason for this delay was concerns about the oncological efficiency” of MIDP in terms of its ability to achieve radical resection and an adequate lymph node yield. At the same time, some concerns about minimally invasive surgery for cancer were raised because of results from randomized trials in other cancer types, such as hysterectomy for cervical cancer. Some studies showed worse survival after minimally invasive surgery than after open surgery.

In recent years, use of minimally invasive techniques for pancreatic cancer has become an increasingly “hot topic in many surgical forums,” Dr. Hilal said.

So his team set out to investigate the approach in a phase 3 noninferiority trial. The investigators focused on patients who had an indication for elective distal pancreatectomy plus splenectomy because of proven or highly suspected pancreatic ductal adenocarcinoma in the pancreatic body or tail.

Patients from 35 centers in 12 countries were recruited between May 2018 and May 2021 and were randomly assigned to undergo either MIDP or open distal pancreatectomy.

Patients, nurses, and pathologists were blinded to the surgical procedure by covering of the abdominal wall.

None of the patients underwent adjuvant or neoadjuvant chemotherapy.

Following the procedure, the patients were followed up at 2 weeks and at 1, 3, 6, and 12 months, and a CT scan was performed at 12 months. A range of assessments was performed at each visit, including quality of life measures.

From 1,146 patients initially screened, 261 patients were included.

A few patients withdrew; 131 patients underwent MIDP, and 127 underwent open surgery and were included in the intention-to-treat analysis. Of those, 129 and 125, respectively, were included in the follow-up analysis.

The results confirmed the noninferiority of MIDP, compared with open surgery, with a rate of R0 radical resection (defined as ≥ 1 mm distance between the tumor and the surgical margin) of 73% vs. 69% (P = .039).

In addition, the lymph node yield was comparable between the two approaches, at an average of 22 nodes for MIDP vs. 23 for open surgery (P = .89), and the time to functional recovery was identical, at 5 days for both (P = .22).

The rate of intraperitoneal recurrence was found to be 41% with MIDP, compared with 38% for patients who underwent open surgery.

Dr. Hilal also showed that the rate of serious adverse events, such as bleeding or organ damage, was similar between the two procedures, at 18% with minimally invasive surgery vs. 22% for the open procedure.

Turning to the survival curves, he noted that it is “very clear” that the two procedures achieved near-identical results, at a hazard ratio of 0.99 (P = .94) for overall survival and 0.97 (P = .88) for disease-free survival when comparing MIDP with open surgery.

The researchers will continue to follow up the patients for 3-5 years and will analyze the lymph nodes retrieved to determine whether removal of the spleen is necessary.

The study was funded by Medtronic and Ethicon. Dr. Hilal has relationships with Ethicon and Medtronic. Dr. Tseng has relationships with Aegerion, Amgen, AstraZeneca, Bristol-Myers Squibb, Cubist, Curadel Surgical Innovations, Daiichi Sankyo/Lilly, GlaxoSmithKline, Intarcia Therapeutics, Merck, MyoKardia, PanTher Therapeutics, Pfizer, Quest Diagnostics, Sanofi, Vertex, and Zeus.

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

French investigators are warning clinicians who treat patients with non–small cell lung cancer (NSCLC) not to initiate treatment with sotorasib within 30 days of an immunotherapy infusion with an anti-programmed cell death–ligand-1 (anti–PD-L1) inhibitor because of the risk of increased toxicity.

Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.

Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.

The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.

The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.

“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.

The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.

The study was published in the Journal of Thoracic Oncology.
 

Actionable findings

“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.

The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”

Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.

Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”

Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”

Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.

Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.

Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”

As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
 

Study details

The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”

Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.

Patients in the study were treated outside of clinical trials at 16 medical centers in France.

Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.

Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.

In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.

The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.

The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.

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

French investigators are warning clinicians who treat patients with non–small cell lung cancer (NSCLC) not to initiate treatment with sotorasib within 30 days of an immunotherapy infusion with an anti-programmed cell death–ligand-1 (anti–PD-L1) inhibitor because of the risk of increased toxicity.

Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.

Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.

The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.

The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.

“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.

The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.

The study was published in the Journal of Thoracic Oncology.
 

Actionable findings

“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.

The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”

Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.

Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”

Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”

Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.

Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.

Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”

As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
 

Study details

The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”

Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.

Patients in the study were treated outside of clinical trials at 16 medical centers in France.

Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.

Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.

In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.

The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.

The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.

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

French investigators are warning clinicians who treat patients with non–small cell lung cancer (NSCLC) not to initiate treatment with sotorasib within 30 days of an immunotherapy infusion with an anti-programmed cell death–ligand-1 (anti–PD-L1) inhibitor because of the risk of increased toxicity.

Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.

Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.

The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.

The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.

“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.

The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.

The study was published in the Journal of Thoracic Oncology.
 

Actionable findings

“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.

The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”

Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.

Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”

Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”

Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.

Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.

Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”

As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
 

Study details

The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”

Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.

Patients in the study were treated outside of clinical trials at 16 medical centers in France.

Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.

Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.

In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.

The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.

The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.

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

The Food and Drug Administration has approved flotufolastat fluorine-18 (Posluma), a radiopharmaceutical for use with PET in prostate cancer.

The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.

Olivier Le Moal/Getty Images

Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.

Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.

Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”

However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
 

Approval based on two single-arm trials

Posluma’s approval was based on two single-arm trials from Blue Earth.

In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.

Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.

“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.

The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.

Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.

Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.

Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).

The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.

The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”

In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”

The labeling for gozetotide carries the same warnings and precautions.

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

The Food and Drug Administration has approved flotufolastat fluorine-18 (Posluma), a radiopharmaceutical for use with PET in prostate cancer.

The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.

Olivier Le Moal/Getty Images

Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.

Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.

Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”

However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
 

Approval based on two single-arm trials

Posluma’s approval was based on two single-arm trials from Blue Earth.

In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.

Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.

“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.

The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.

Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.

Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.

Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).

The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.

The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”

In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”

The labeling for gozetotide carries the same warnings and precautions.

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

The Food and Drug Administration has approved flotufolastat fluorine-18 (Posluma), a radiopharmaceutical for use with PET in prostate cancer.

The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.

Olivier Le Moal/Getty Images

Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.

Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.

Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”

However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
 

Approval based on two single-arm trials

Posluma’s approval was based on two single-arm trials from Blue Earth.

In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.

Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.

“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.

The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.

Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.

Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.

Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).

The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.

The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”

In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”

The labeling for gozetotide carries the same warnings and precautions.

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

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The federal government is reconsidering a decision that breast cancer patients, plastic surgeons, and members of Congress have protested would limit women’s options for reconstructive surgery.

On June 1, the Centers for Medicare & Medicaid Services plans to reexamine how doctors are paid for a type of breast reconstruction known as DIEP flap, in which skin, fat, and blood vessels are harvested from a woman’s abdomen to create a new breast.

The procedure offers potential advantages over implants and operations that take muscle from the abdomen. But it’s also more expensive. If patients go outside an insurance network for the operation, it can cost more than $50,000. And, if insurers pay significantly less for the surgery as a result of the government’s decision, some in-network surgeons would stop offering it, a plastic surgeons group has argued.

The DIEP flap controversy, spotlighted by CBS News in January, illustrates arcane and indirect ways the federal government can influence which medical options are available – even to people with private insurance. Often, the answers come down to billing codes – which identify specific medical services on forms doctors submit for reimbursement – and the competing pleas of groups whose interests are riding on them.

Medical coding is the backbone for “how business gets done in medicine,” said Karen Joynt Maddox, MD, MPH, a physician at Washington University in St. Louis who researches health economics and policy.

CMS, the agency overseeing Medicare and Medicaid, maintains a list of codes representing thousands of medical services and products. It regularly evaluates whether to add codes or revise or remove existing ones. In 2022, it decided to eliminate a code that has enabled doctors to collect much more money for DIEP flap operations than for simpler types of breast reconstruction.

In 2006, CMS established an “S” code – S2068 – for what was then a relatively new procedure: breast reconstructions with deep inferior epigastric perforator flap (DIEP flap). S codes temporarily fill gaps in a parallel system of billing codes known as CPT codes, which are maintained by the American Medical Association.

Codes don’t dictate the amounts private insurers pay for medical services; those reimbursements are generally worked out between insurance companies and medical providers. However, using the narrowly targeted S code, doctors and hospitals have been able to distinguish DIEP flap surgeries, which require complex microsurgical skills, from other forms of breast reconstruction that take less time to perform and generally yield lower insurance reimbursements.

CMS announced in 2022 that it planned to eliminate the S code at the end of 2024 – a move some doctors say would slash the amount surgeons are paid. (To be precise, CMS announced it would eliminate a series of three S codes for similar procedures, but some of the more outspoken critics have focused on one of them, S2068.) The agency’s decision is already changing the landscape of reconstructive surgery and creating anxiety for breast cancer patients.

Kate Getz, a single mother in Morton, Ill., learned she had cancer in January at age 30. As she grappled with her diagnosis, it was overwhelming to think about what her body would look like over the long term. She pictured herself getting married one day and wondered “how on earth I would be able to wear a wedding dress with only having one breast left,” she said.

She thought a DIEP flap was her best option and worried about having to undergo repeated surgeries if she got implants instead. Implants generally need to be replaced every 10 years or so. But after she spent more than a month trying to get answers about how her DIEP flap surgery would be covered, Ms. Getz’s insurer, Cigna, informed her it would use a lower-paying CPT code to reimburse her physician, Ms. Getz said. As far as she could see, that would have made it impossible for Ms. Getz to obtain the surgery.

Paying out of pocket was “not even an option.”

“I’m a single mom. We get by, right? But I’m not, not wealthy by any means,” she said.

Cost is not necessarily the only hurdle patients seeking DIEP flaps must overcome. Citing the complexity of the procedure, Ms. Getz said, a local plastic surgeon told her it would be difficult for him to perform. She ended up traveling from Illinois to Texas for the surgery.

The government’s plan to eliminate the three S codes was driven by the Blue Cross Blue Shield Association, a major lobbying organization for health insurance companies. In 2021, the group asked CMS to discontinue the codes, arguing that they were no longer needed because the AMA had updated a CPT code to explicitly include DIEP flap surgery and the related operations, according to a CMS document.

For years, the AMA advised doctors that the CPT code was appropriate for DIEP flap procedures. But after the government’s decision, at least two major insurance companies told doctors they would no longer reimburse them under the higher-paying codes, prompting a backlash.

Physicians and advocacy groups for breast cancer patients, such as the nonprofit organization Susan G. Komen, have argued that many plastic surgeons would stop providing DIEP flap procedures for women with private insurance because they wouldn’t get paid enough.

Lawmakers from both parties have asked the agency to keep the S code, including Rep. Debbie Wasserman Schultz (D-Fla.) and Sen. Amy Klobuchar (D-Minn.), who have had breast cancer, and Sen. Marsha Blackburn (R-Tenn.).

CMS at its June 1 meeting will consider whether to keep the three S codes or delay their expiration.

In a May 30 statement, Blue Cross Blue Shield Association spokesperson Kelly Parsons reiterated the organization’s view that “there is no longer a need to keep the S codes.”

In a profit-driven health care system, there’s a tug of war over reimbursements between providers and insurance companies, often at the expense of patients, said Dr. Joynt Maddox.

“We’re in this sort of constant battle” between hospital chains and insurance companies “about who’s going to wield more power at the bargaining table,” Dr. Joynt Maddox said. “And the clinical piece of that often gets lost, because it’s not often the clinical benefit and the clinical priority and the patient centeredness that’s at the middle of these conversations.”

Elisabeth Potter, MD, a plastic surgeon who specializes in DIEP flap surgeries, decided to perform Ms. Getz’s surgery at whatever price Cigna would pay.

According to Fair Health, a nonprofit that provides information on health care costs, in Austin, Tex. – where Dr. Potter is based – an insurer might pay an in-network doctor $9,323 for the surgery when it’s billed using the CPT code and $18,037 under the S code. Those amounts are not averages; rather, Fair Health estimated that 80% of payment rates are lower than or equal to those amounts.

Dr. Potter said her Cigna reimbursement “is significantly lower.”

Weeks before her May surgery, Ms. Getz received big news – Cigna had reversed itself and would cover her surgery under the S code. It “felt like a real victory,” she said.

But she still fears for other patients.

“I’m still asking these companies to do right by women,” Ms. Getz said. “I’m still asking them to provide the procedures we need to reimburse them at rates where women have access to them regardless of their wealth.”

In a statement, Cigna spokesperson Justine Sessions said the insurer remains “committed to ensuring that our customers have affordable coverage and access to the full range of breast reconstruction procedures and to quality surgeons who perform these complex surgeries.”

Medical costs that health insurers cover generally are passed along to consumers in the form of premiums, deductibles, and other out-of-pocket expenses.

For any type of breast reconstruction, there are benefits, risks, and trade-offs. A 2018 paper published in JAMA Surgery found that women who underwent DIEP flap surgery had higher odds of developing “reoperative complications” within 2 years than those who received artificial implants. However, DIEP flaps had lower odds of infection than implants.

Implants carry risks of additional surgery, pain, rupture, and even an uncommon type of immune system cancer.

Other flap procedures that take muscle from the abdomen can leave women with weakened abdominal walls and increase their risk of developing a hernia.

Academic research shows that insurance reimbursement affects which women can access DIEP flap breast reconstruction, creating a two-tiered system for private health insurance versus government programs like Medicare and Medicaid. Private insurance generally pays physicians more than government coverage, and Medicare doesn’t use S codes.

Lynn Damitz, a physician and board vice president of health policy and advocacy for the American Society of Plastic Surgeons, said the group supports continuing the S code temporarily or indefinitely. If reimbursements drop, some doctors won’t perform DIEP flaps anymore.

A study published in February found that, of patients who used their own tissue for breast reconstruction, privately insured patients were more likely than publicly insured patients to receive DIEP flap reconstruction.

To Dr. Potter, that shows what will happen if private insurance payments plummet. “If you’re a Medicare provider and you’re not paid to do DIEP flaps, you never tell a patient that it’s an option. You won’t perform it,” Dr. Potter said. “If you take private insurance and all of a sudden your reimbursement rate is cut from $15,000 down to $3,500, you’re not going to do that surgery. And I’m not saying that that’s the right thing to do, but that’s what happens.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Paula Ngon, a 28-year-old public relations professional with Estée Lauder in New York, understands the value of good communication. After all, it’s her job to share information about her employer’s products with the world. Recently, she needed to tap her career training for another purpose: to capture the attention of a heedless oncologist.

Diagnosed with Hodgkin lymphoma in 2021, Ms. Ngon underwent port surgery to allow chemotherapy to be administered. Her right arm lost circulation and went numb, so she sought guidance from her blood cancer specialist. He dismissed her worries, saying that her tumors were pinching a nerve. She’d get better, he predicted, after more chemo.

credit to Paula Ngon

“I knew in my body that something was wrong,” Ms. Ngon recalled. When the oncologist continued to downplay her concerns, she and a fellow communications specialist sat down together in the hospital lobby to draft an email to her physician. “We were trying to articulate the urgency in an email that expresses that I’m not being dramatic. We had to do it in a way that didn’t insult his intelligence: ‘Respectfully, you’re the doctor, but I know something is wrong.’ ”

In essence, Ms. Ngon was trying to be diplomatic and not trigger her oncologist’s defenses, while still convincing him to take action. Her approach to getting her doctor’s attention worked. He referred Ms. Ngon to a radiologist, who discovered that she had blood clots in her arm. Ms. Ngon then landed in the ICU for a week, as clinicians tried to break up the clots.

“I was the perfect person for this to happen to, because of my job and education. But it makes me sad because I understand I was in a fortunate position, with a background in communication. Most people don’t have that,” Ms. Ngon said.

This and other negative experiences during her medical saga inspired Ms. Ngon to partner with the Lymphoma Research Foundation in order to spread the word about unique challenges facing patients like her: people of color.

Ms. Ngon, who is Black, said her goal as a patient advocate is to “empower communities of color to speak up for themselves and hold oncologists responsible for listening and understanding differences across cultures.” And she wants to take a stand against the “gaslighting” of patients.

African Americans with hematologic disease like Ms. Ngon face a higher risk of poor outcomes than Whites, even as they are less likely than Whites to develop certain blood cancers. The reasons for this disparity aren’t clear, but researchers suspect they’re related to factors such as poverty, lack of insurance, genetics, and limited access to high-quality care.

Some researchers have blamed another factor: racism. A 2022 study sought to explain why Black and Hispanic patients with acute myeloid leukemia in urban areas have higher mortality rates than Whites, “despite more favorable genetics and younger age” (hazard ratio, 1.59, 95% confidence interval, 1.15-2.22 and HR, 1.25; 95% CI, 0.88-1.79). The study authors determined that “structural racism” – which they measured by examining segregation and “disadvantage” in neighborhoods where patients lived – accounted for nearly all of the disparities.

Ms. Ngon said her experiences and her awareness about poorer outcomes in medicine for African Americans – such as higher death rates for Black women during pregnancy – affect how she interacts with clinicians. “I automatically assume a barrier between me and my doctors, and it’s their responsibility to dismantle it.”

Making an connection with a physician can make a huge difference, she said. “I walked into my primary care doctor’s office and saw that she was a Latino woman. My guard went down, and I could feel her care for me as a human being. Whether that was because she was also a woman of color or not, I don’t know. But I did feel more cared for.”

However, Ms. Ngon could not find a Black oncologist to care for her in New York City, and that’s no surprise.

Ethnic and gender diversity remains an immense challenge in the hematology/oncology field. According to the American Society of Clinical Oncology, only about a third of oncologists are women, and the percentages identifying themselves as Black/African American and Hispanic are just 2.3% and 5.8%, respectively.

These numbers don’t seem likely to budge much any time soon. An analysis of medical students in U.S. oncology training programs from 2015-2020 found that just 3.8% identified themselves as Black/African American and 5.1% as Hispanic/Latino versus 52.15% as White and 31% as Asian/Pacific Islander/Native Hawaiian.

Ms. Ngon encountered challenges on other fronts during her cancer care. When she needed a wig during chemotherapy, a list of insurer-approved shops didn’t include any that catered to African Americans. Essentially, she said, she was being told that she couldn’t “purchase a wig from a place that makes you feel comfortable and from a woman who understand your needs as a Black woman. It needs to be from these specific shops that really don’t cater to my community.”

She also found it difficult to find fellow patients who shared her unique challenges. “I remember when I was diagnosed, I was looking through the support groups on Facebook, trying to find someone Black to ask about whether braiding my hair might stop it from falling out.”

Now, Ms. Ngon is in remission. And she’s happy with her oncologist, who’s White. “He listened to me, and he promised me that I would have the most boring recovery process ever, after everything I’d experienced. That explains a lot of why I felt so comfortable with him.”

She hopes to use her partnership with the Lymphoma Research Foundation to be a resource for people of color and alert them to the support that’s available for them. “I would love to let them know how to advocate for themselves as patients, how to trust their bodies, how to push back if they feel like they’re not getting the care that they deserve.”

Ms. Ngon would also like to see more support for medical students of color. “I hope to exist in a world one day where it wouldn’t be so hard to find an oncologist who looks like me in a city as large as this one,” she said.

As for oncologists, she urged them to “go the extra mile and really, really listen to what patients are saying. It’s easier said than done because there are natural biases in this world, and it’s hard to overcome those obstacles. But to not be heard and have to push every time. It was just exhausting to do that on top of trying to beat cancer.”

Paula Ngon, a 28-year-old public relations professional with Estée Lauder in New York, understands the value of good communication. After all, it’s her job to share information about her employer’s products with the world. Recently, she needed to tap her career training for another purpose: to capture the attention of a heedless oncologist.

Diagnosed with Hodgkin lymphoma in 2021, Ms. Ngon underwent port surgery to allow chemotherapy to be administered. Her right arm lost circulation and went numb, so she sought guidance from her blood cancer specialist. He dismissed her worries, saying that her tumors were pinching a nerve. She’d get better, he predicted, after more chemo.

credit to Paula Ngon

“I knew in my body that something was wrong,” Ms. Ngon recalled. When the oncologist continued to downplay her concerns, she and a fellow communications specialist sat down together in the hospital lobby to draft an email to her physician. “We were trying to articulate the urgency in an email that expresses that I’m not being dramatic. We had to do it in a way that didn’t insult his intelligence: ‘Respectfully, you’re the doctor, but I know something is wrong.’ ”

In essence, Ms. Ngon was trying to be diplomatic and not trigger her oncologist’s defenses, while still convincing him to take action. Her approach to getting her doctor’s attention worked. He referred Ms. Ngon to a radiologist, who discovered that she had blood clots in her arm. Ms. Ngon then landed in the ICU for a week, as clinicians tried to break up the clots.

“I was the perfect person for this to happen to, because of my job and education. But it makes me sad because I understand I was in a fortunate position, with a background in communication. Most people don’t have that,” Ms. Ngon said.

This and other negative experiences during her medical saga inspired Ms. Ngon to partner with the Lymphoma Research Foundation in order to spread the word about unique challenges facing patients like her: people of color.

Ms. Ngon, who is Black, said her goal as a patient advocate is to “empower communities of color to speak up for themselves and hold oncologists responsible for listening and understanding differences across cultures.” And she wants to take a stand against the “gaslighting” of patients.

African Americans with hematologic disease like Ms. Ngon face a higher risk of poor outcomes than Whites, even as they are less likely than Whites to develop certain blood cancers. The reasons for this disparity aren’t clear, but researchers suspect they’re related to factors such as poverty, lack of insurance, genetics, and limited access to high-quality care.

Some researchers have blamed another factor: racism. A 2022 study sought to explain why Black and Hispanic patients with acute myeloid leukemia in urban areas have higher mortality rates than Whites, “despite more favorable genetics and younger age” (hazard ratio, 1.59, 95% confidence interval, 1.15-2.22 and HR, 1.25; 95% CI, 0.88-1.79). The study authors determined that “structural racism” – which they measured by examining segregation and “disadvantage” in neighborhoods where patients lived – accounted for nearly all of the disparities.

Ms. Ngon said her experiences and her awareness about poorer outcomes in medicine for African Americans – such as higher death rates for Black women during pregnancy – affect how she interacts with clinicians. “I automatically assume a barrier between me and my doctors, and it’s their responsibility to dismantle it.”

Making an connection with a physician can make a huge difference, she said. “I walked into my primary care doctor’s office and saw that she was a Latino woman. My guard went down, and I could feel her care for me as a human being. Whether that was because she was also a woman of color or not, I don’t know. But I did feel more cared for.”

However, Ms. Ngon could not find a Black oncologist to care for her in New York City, and that’s no surprise.

Ethnic and gender diversity remains an immense challenge in the hematology/oncology field. According to the American Society of Clinical Oncology, only about a third of oncologists are women, and the percentages identifying themselves as Black/African American and Hispanic are just 2.3% and 5.8%, respectively.

These numbers don’t seem likely to budge much any time soon. An analysis of medical students in U.S. oncology training programs from 2015-2020 found that just 3.8% identified themselves as Black/African American and 5.1% as Hispanic/Latino versus 52.15% as White and 31% as Asian/Pacific Islander/Native Hawaiian.

Ms. Ngon encountered challenges on other fronts during her cancer care. When she needed a wig during chemotherapy, a list of insurer-approved shops didn’t include any that catered to African Americans. Essentially, she said, she was being told that she couldn’t “purchase a wig from a place that makes you feel comfortable and from a woman who understand your needs as a Black woman. It needs to be from these specific shops that really don’t cater to my community.”

She also found it difficult to find fellow patients who shared her unique challenges. “I remember when I was diagnosed, I was looking through the support groups on Facebook, trying to find someone Black to ask about whether braiding my hair might stop it from falling out.”

Now, Ms. Ngon is in remission. And she’s happy with her oncologist, who’s White. “He listened to me, and he promised me that I would have the most boring recovery process ever, after everything I’d experienced. That explains a lot of why I felt so comfortable with him.”

She hopes to use her partnership with the Lymphoma Research Foundation to be a resource for people of color and alert them to the support that’s available for them. “I would love to let them know how to advocate for themselves as patients, how to trust their bodies, how to push back if they feel like they’re not getting the care that they deserve.”

Ms. Ngon would also like to see more support for medical students of color. “I hope to exist in a world one day where it wouldn’t be so hard to find an oncologist who looks like me in a city as large as this one,” she said.

As for oncologists, she urged them to “go the extra mile and really, really listen to what patients are saying. It’s easier said than done because there are natural biases in this world, and it’s hard to overcome those obstacles. But to not be heard and have to push every time. It was just exhausting to do that on top of trying to beat cancer.”

Paula Ngon, a 28-year-old public relations professional with Estée Lauder in New York, understands the value of good communication. After all, it’s her job to share information about her employer’s products with the world. Recently, she needed to tap her career training for another purpose: to capture the attention of a heedless oncologist.

Diagnosed with Hodgkin lymphoma in 2021, Ms. Ngon underwent port surgery to allow chemotherapy to be administered. Her right arm lost circulation and went numb, so she sought guidance from her blood cancer specialist. He dismissed her worries, saying that her tumors were pinching a nerve. She’d get better, he predicted, after more chemo.

credit to Paula Ngon

“I knew in my body that something was wrong,” Ms. Ngon recalled. When the oncologist continued to downplay her concerns, she and a fellow communications specialist sat down together in the hospital lobby to draft an email to her physician. “We were trying to articulate the urgency in an email that expresses that I’m not being dramatic. We had to do it in a way that didn’t insult his intelligence: ‘Respectfully, you’re the doctor, but I know something is wrong.’ ”

In essence, Ms. Ngon was trying to be diplomatic and not trigger her oncologist’s defenses, while still convincing him to take action. Her approach to getting her doctor’s attention worked. He referred Ms. Ngon to a radiologist, who discovered that she had blood clots in her arm. Ms. Ngon then landed in the ICU for a week, as clinicians tried to break up the clots.

“I was the perfect person for this to happen to, because of my job and education. But it makes me sad because I understand I was in a fortunate position, with a background in communication. Most people don’t have that,” Ms. Ngon said.

This and other negative experiences during her medical saga inspired Ms. Ngon to partner with the Lymphoma Research Foundation in order to spread the word about unique challenges facing patients like her: people of color.

Ms. Ngon, who is Black, said her goal as a patient advocate is to “empower communities of color to speak up for themselves and hold oncologists responsible for listening and understanding differences across cultures.” And she wants to take a stand against the “gaslighting” of patients.

African Americans with hematologic disease like Ms. Ngon face a higher risk of poor outcomes than Whites, even as they are less likely than Whites to develop certain blood cancers. The reasons for this disparity aren’t clear, but researchers suspect they’re related to factors such as poverty, lack of insurance, genetics, and limited access to high-quality care.

Some researchers have blamed another factor: racism. A 2022 study sought to explain why Black and Hispanic patients with acute myeloid leukemia in urban areas have higher mortality rates than Whites, “despite more favorable genetics and younger age” (hazard ratio, 1.59, 95% confidence interval, 1.15-2.22 and HR, 1.25; 95% CI, 0.88-1.79). The study authors determined that “structural racism” – which they measured by examining segregation and “disadvantage” in neighborhoods where patients lived – accounted for nearly all of the disparities.

Ms. Ngon said her experiences and her awareness about poorer outcomes in medicine for African Americans – such as higher death rates for Black women during pregnancy – affect how she interacts with clinicians. “I automatically assume a barrier between me and my doctors, and it’s their responsibility to dismantle it.”

Making an connection with a physician can make a huge difference, she said. “I walked into my primary care doctor’s office and saw that she was a Latino woman. My guard went down, and I could feel her care for me as a human being. Whether that was because she was also a woman of color or not, I don’t know. But I did feel more cared for.”

However, Ms. Ngon could not find a Black oncologist to care for her in New York City, and that’s no surprise.

Ethnic and gender diversity remains an immense challenge in the hematology/oncology field. According to the American Society of Clinical Oncology, only about a third of oncologists are women, and the percentages identifying themselves as Black/African American and Hispanic are just 2.3% and 5.8%, respectively.

These numbers don’t seem likely to budge much any time soon. An analysis of medical students in U.S. oncology training programs from 2015-2020 found that just 3.8% identified themselves as Black/African American and 5.1% as Hispanic/Latino versus 52.15% as White and 31% as Asian/Pacific Islander/Native Hawaiian.

Ms. Ngon encountered challenges on other fronts during her cancer care. When she needed a wig during chemotherapy, a list of insurer-approved shops didn’t include any that catered to African Americans. Essentially, she said, she was being told that she couldn’t “purchase a wig from a place that makes you feel comfortable and from a woman who understand your needs as a Black woman. It needs to be from these specific shops that really don’t cater to my community.”

She also found it difficult to find fellow patients who shared her unique challenges. “I remember when I was diagnosed, I was looking through the support groups on Facebook, trying to find someone Black to ask about whether braiding my hair might stop it from falling out.”

Now, Ms. Ngon is in remission. And she’s happy with her oncologist, who’s White. “He listened to me, and he promised me that I would have the most boring recovery process ever, after everything I’d experienced. That explains a lot of why I felt so comfortable with him.”

She hopes to use her partnership with the Lymphoma Research Foundation to be a resource for people of color and alert them to the support that’s available for them. “I would love to let them know how to advocate for themselves as patients, how to trust their bodies, how to push back if they feel like they’re not getting the care that they deserve.”

Ms. Ngon would also like to see more support for medical students of color. “I hope to exist in a world one day where it wouldn’t be so hard to find an oncologist who looks like me in a city as large as this one,” she said.

As for oncologists, she urged them to “go the extra mile and really, really listen to what patients are saying. It’s easier said than done because there are natural biases in this world, and it’s hard to overcome those obstacles. But to not be heard and have to push every time. It was just exhausting to do that on top of trying to beat cancer.”

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

The first-in-class erythroid maturation agent luspatercept showed significant improvement over the erythropoiesis-stimulating agent epoetin alfa in reducing dependency on red blood cell transfusions among patients with lower-risk myelodysplastic syndromes (LR-MDS) who are ESA naive.

“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.

“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.

Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.

“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.

“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.

In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.

Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.

While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.

Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.

In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.

To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.

For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.

Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.

For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).

In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).

Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.

Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).

The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.

In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.

Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).

“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.

Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”

“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.

Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.

“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”

“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.

“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.

The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.

The first-in-class erythroid maturation agent luspatercept showed significant improvement over the erythropoiesis-stimulating agent epoetin alfa in reducing dependency on red blood cell transfusions among patients with lower-risk myelodysplastic syndromes (LR-MDS) who are ESA naive.

“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.

“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.

Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.

“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.

“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.

In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.

Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.

While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.

Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.

In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.

To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.

For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.

Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.

For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).

In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).

Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.

Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).

The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.

In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.

Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).

“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.

Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”

“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.

Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.

“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”

“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.

“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.

The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.

The first-in-class erythroid maturation agent luspatercept showed significant improvement over the erythropoiesis-stimulating agent epoetin alfa in reducing dependency on red blood cell transfusions among patients with lower-risk myelodysplastic syndromes (LR-MDS) who are ESA naive.

“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.

“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.

Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.

“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.

“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.

In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.

Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.

While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.

Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.

In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.

To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.

For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.

Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.

For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).

In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).

Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.

Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).

The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.

In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.

Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).

“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.

Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”

“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.

Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.

“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”

“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.

“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.

The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.