FDA Advisors Set to Consider Stomach Cancer Restrictions for Yervoy, Opdivo, Keytruda

A panel of outside advisors to the U.S. Food and Drug Administration (FDA) are scheduled to meet next month, to review whether recent scientific findings about the potential side effects of Opdivo, Keytruda and Yervoy warrant restrictions on use of the class drugs used for the treatment of stomach cancer.

Opdivo (nivolumab), Yervoy (ipilimumab) and Keytruda (pembrolizumab) all belong to a class of medications known as PD-1 inhibitors, which are designed to prevent the immune system from attacking healthy cells in the body. The drugs are widely approved for a number of cancer treatments, but research has suggested the drugs only decrease the risk of death for stomach cancer patients by about 20%, when compared to chemotherapy.

In a Federal Register notice (PDF) officially released today, the U.S. Food and Drug Administration (FDA) has announced it will convene a meeting of its Oncologic Drugs Advisory Committee (ODAC) on September 26. The advisory committee will examine the scientific data on the drugs and report back to the agency on whether the entire class of medications should be limited in their applications for stomach cancer treatment.

While the advisory committee’s recommendations are not binding, they usually have significant influence on the FDA’s regulatory decisions.

“The current labeling for approved checkpoint inhibitors in this indication reflects broad approvals in the intent to treat patient populations agnostic of programmed death cell ligand-1 (PD-L1) expression,” the FDA notice states. “Cumulative data have shown that PD-L1 expression appears to be a predictive biomarker of treatment efficacy in this patient population; however, clinical trials have used different approaches to assess PD-L1 expression and different thresholds to define PD-L1 positivity.”

Cancer Drug Side Effect Concerns

The advisory panel will weigh the pros and cons of PD-1 inhibitor cancer treatments, looking at the drugs’ risks compared to their potential benefits for stomach cancer patients.

The drugs, also known as immune checkpoint inhibitors, have been linked to a number of adverse side effects in recent years.

In August 2017, a study published in the medical journal JAMA Oncology warned that as many as nine out of 10 patients given the drug combo of Opdivo and Yervoy suffered significant immune-related adverse events.

The study found that 91% of the patients had clinically significant immune-related adverse events and 72% of the patients needed systemic steroid treatment. In addition, half of the patients had an emergency room visit, 11% developed hyperglycemia, and more than a third required hospital admission due to immune-related adverse events.

A short time later, the FDA issued a safety alert about two Keytruda studies on August 31, 2017, after finding an increased risk of death when the drug is used in combination with some other medications to treat multiple myeloma.

A month later, in September 2017, the FDA announced it was halting Opdivo clinical trials testing the drug in conjunction with Celgene’s Revlimid or Pomalyst medications, which are the same medications used in conjunction with Keytruda, due to the previous multiple myeloma patient deaths.

Last year, Merck voluntarily requested that Keytruda’s approvals be restricted as a first-line treatment for HER2-positive gastric and GEJ cancer to PD-L1-positive tumors only.

Advisory Committee Meeting Public Participation

The FDA ODAC advisory committee will meet on September 26, 2024, at the FDA’s White Oak Campus in Silver Spring, Maryland. The agency indicates that the public will have the opportunity to participate, and that the meeting will be available through online teleconferencing and video conferencing platforms.

Those with questions about attending the meeting can obtain more information by visiting: https://www.fda.gov/AdvisoryCommittees/AboutAdvisoryCommittees/ucm408555.htm

The agency is also accepting and considering public comments until September 25, but only those received by September 12 will be provided to the Committee. Information on how to submit comments is available in the FDA federal register notice.