FDA Puts New Stomach Cancer Restrictions in Place for Keytruda, Opdivo

Recommendations made by a scientific advisory panel last year have been embraced by federal regulators.

Federal drug regulators have decided to place new limits on the use of autoimmune medications Keytruda and Opdivo for stomach cancer, after scientific experts determined there is insufficient evidence to prove they are effective.

Late last month, the U.S. Food and Drug Administration (FDA) sent letters to Merck (PDF), the makers of Keytruda (pembrolizumab), and Bristol-Myers Squibb (PDF), the manufacturers of Opdivo (nivolumab), indicating the agency was placing new restrictions on those drugs, which belong to a class of medications known as PD-1 inhibitors.

PD-1 inhibitors are designed to prevent the immune system from attacking healthy cells in the body. The drugs have been widely approved for a number of cancer treatments as well.

However, research has suggested that the drugs only decrease the risk of death from stomach cancer by about 20%, when compared to chemotherapy. As a result, the FDA Oncologic Drugs Advisory Committee voted 10-2 to recommend limitations on the drugs in September 2024, after determining there are no indications of successful treatment of patients with PD-L1 negative tumors, a subset of tumors the drugs are designed to treat.

The committee was tasked with examining scientific data on Opdivo, Keytruda and other PD-1 drugs to determine whether the entire class of medications should be limited in their use for the treatment of stomach cancer. One member of the committee abstained from the vote.

The agency appears to have decided to follow the advisory committee’s advice, limiting the use of these medications for stomach cancer treatment to advanced or metastatic stomach cancers with positive PD-L1 expression. The letters to the two manufacturers indicate there will need to be updates to the Prescribing Information and Medication Guides announcing the new limits on use.

The companies have filed revisions to the drugs’ existing indications after their arguments for broader-use labels were rejected.

The lack of stomach cancer effectiveness in certain cases is only one of a number of concerns over PD-L1 treatments. 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.

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

Last year, before the FDA advisory committee meeting and vote, 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.