FDA Advisors Vote for Restrictions on Opdivo, Keytruda, Similar Stomach Cancer Drugs

Panel of independent experts found little to no evidence that these drugs extend the lives of stomach cancer patients.

A panel of scientific advisors say the government should put more restrictions on stomach cancer drugs like Keytruda, Opdivo and Yervoy, particularly for patients with certain types of tumors, due to a lack of evidence to establish the treatments are effective.

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 medications only decrease the risk of death for stomach cancer patients by about 20%, when compared to chemotherapy.

On September 26, the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 10-2 that PD-1 drugs did not have favorable results when taken by patients with PD-L1 negative tumors, which are a subset of tumors that the drugs have been designed to treat.

The committee was tasked with examining scientific data on Opdivo, Yervoy, 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.

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

The panel’s findings seem to back up data from the FDA’s own reviewers, which released an analysis of clinical trials for Opdivo and Keytruda, which determined that their life-extending benefits did not appear to include those with PD-L1 negative tumors. However, the drugs did not show an increase in mortality among those patients.

The manufacturers have argued that limiting access to PD-1 drugs, which are first-line cancer treatments, could exclude some PD-L1 negative tumor patients who may benefit, but those who voted for restrictions said there was no evidence of any benefit.

PD-1 Stomach Cancer Drug Concerns

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.

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.

It is unclear when the FDA will render a final decision on whether to restrict the drugs, but such a decision is seen as likely.