Managing shifts in treatment
In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.
Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.
Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.
“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”
Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.
“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
#ProjectFacilitate for expanded access
One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.
A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.
“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.
“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.
Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.
ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.
“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.
But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.
“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.
ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.
“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.
He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.
His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.
“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.
Close split on nivolumab
In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.
ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.
“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.
ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.
A version of this article first appeared on Medscape.com.