On the first day of a historic three-day meeting into cancer indications that were granted an accelerated approval by the Food and Drug Administration (FDA), the first one to come under discussion is staying in place, at least for now.
Members of the FDA's Oncologic Drugs Advisory Committee (ODAC) voted 7-2 in favor of keeping in place the indication for atezolizumab (Tecentriq) for use in a certain form of breast cancer, and at the same time urging the manufacturer, Genentech, to do the research needed to prove the medicine works for these patients.
The specific indication is for atezolizumab use as part of a combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors are PD-L1+.
The FDA granted a conditional clearance known as an accelerated approval in 2019 for this use of atezolizumab, expecting Genentech to produce more extensive evidence of this benefit. But so far, Genentech has not produced the data proving to the FDA that atezolizumab provides the expected benefit.
The drug was already available for use in bladder cancer, having been granted an accelerated approval for this indication in 2016. (This indication will be discussed on day two of the meeting.)
Other Accelerated Approvals Withdrawn
This week's three-day ODAC meeting is part of the FDA's broader reconsideration of what it has described as "dangling accelerated approvals."
Earlier discussion between the FDA and drugmakers have already triggered four voluntary withdrawals of cancer indications with these accelerated approvals, noted Julia A. Beaver, MD, and Richard Pazdur, MD, two of the FDA's top regulators of oncology medicine, in an April 21 perspective article in the New England Journal of Medicine.
"The small percentage of drugs whose clinical benefit is ultimately not confirmed should be viewed not as a failure of accelerated approval but rather as an expected trade-off in expediting drug development that benefits patients with severe or life-threatening diseases," Beaver and Pazdur write.
But making these calls can be tough. On the first day of the meeting, even ODAC panelists who backed Genentech's bid to maintain an mTNBC indication for atezolizumab expressed discomfort with this choice.
The FDA granted the accelerated approval for use of this drug in March 2019 based upon improved progression-free survival from the IMpassion130 trial. But the drug fell short in subsequent efforts to confirm the results seen in that study. The confirmatory IMpassion131 trial failed to meet the primary endpoint, the FDA staff noted in briefing materials for the ODAC meeting.
ODAC panelist Stan Lipkowitz, MD, PhD, of the National Cancer Institute (NCI), said he expected this vote had been a tough one for all members serving on ODAC that day.
"In some ways, the purist in me said I should have voted no. But when I looked at the data, there are a couple of things that struck me," said Lipkowitz, who is the chief of the Women's Malignancies Branch at NCI's Center for Cancer Research. “First of all the landscape hasn't changed. There's really no therapy in the first line for triple-negative metastatic that is shown to improve survival.”
Lipkowitz emphasized that Genentech needs to continue to try to prove atezolizumab works in this setting.
"There needs to be confirmatory study," Lipkowitz concluded.
ODAC panelist Matthew Ellis, MD, PhD, of Baylor College of Medicine in Houston, Texas, said he also understood the difficult outlook for women fighting this cancer, but he voted against maintaining the approval.
"It's not that I don't feel the tragedy of these women," said Ellis, citing his own decades of clinical experience.
"I just think that the data are the data," Ellis said, adding that in his view, the "the only correct interpretation" of the evidence supported a vote against allowing the indication to stay.
The FDA considers the recommendations of its advisory committees, but is not bound by them.
In a statement issued after the vote, Genentech said it intends to work with the FDA to determine the next steps for this indication of atezolizumab because "the clinically meaningful benefit demonstrated in the IMpassion130 study remains."
The ODAC meeting continues for 2 more days, and will consider five more cancer indications that have been granted an accelerated approval.
Kerry Dooley Young is a freelance journalist based in Washington, D.C. She earlier covered health policy and the federal budget for Congressional Quarterly/CQ Roll Call and the pharmaceutical industry and the Food and Drug Administration for Bloomberg. Follow her on Twitter @kdooleyyoung.
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Cite this: FDA Panel Backs Atezolizumab for mTNBC -- at Least for Now - Medscape - Apr 28, 2021.