FDA to Evaluate Status of 6 Cancer Drug Indications That Were Granted Accelerated Approvals

Six indications for multiple immune checkpoint inhibitors to treat various cancers are going to be reassessed, according to the Food and Drug Administration (FDA).

The agency previously granted the therapies accelerated approval, but confirmatory clinical trials assessing their continued effectiveness have since failed.

As a result, the FDA’s Oncologic Drugs Advisory Committee has scheduled a special three-day public hearing from April 27 to April 29 to allow patient testimony and expert commentary about the drugs in question. Once the meeting is completed, the committee will consider whether the approvals of the drugs — which are being used to treat triple-negative breast cancer, metastatic urothelial carcinoma, gastric cancers and hepatocellular carcinoma — should be withdrawn and whether further study is needed.

The indications that are under review include:

• Tecentriq (atezolizumab) – plus Abraxane (nab-paclitaxel) to treat patients with PD-L1–positive unresectable locally advanced or metastatic triple-negative breast cancer; and as a single-agent treatment for patients with locally advanced or metastatic urothelial carcinoma who are ineligible to receive cisplatin-containing chemotherapy.
• Keytruda (pembrolizumab) – as a single-agent therapy for patients with locally advanced or metastatic urothelial carcinoma who are ineligible to receive cisplatin-containing chemotherapy; for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma that express PD-L1 and has progressed after two or more previous lines of therapy; and for patients with hepatocellular carcinoma previously treated with Nexavar (sorafenib).
• Opdivo (nivolumab) – as a single agent for patients with hepatocellular carcinoma who previously received Nexavar.

The hearings come after several drug manufacturers recently started withdrawing cancer drug indications voluntarily.

As a part of the influx of withdrawals, Bristol-Myers Squibb announced it had withdrawn Opdivo’s indication for the treatment of small cell lung cancer in January. Moreover, Merck recently announced it would pull Keytruda’s indication for the treatment of patients with metastatic small cell lung cancer whose disease progressed on or after platinum-based chemotherapy and one or more prior line of therapy.

Drugs are granted accelerated approval in instances where they treat serious medical conditions and would help fulfill an unmet need based on a surrogate endpoint. However, drug manufacturers are then required to continue conducting trials that confirm a benefit. If deemed successful, the agency grants the drug a full approval.

“We are committed to ensuring the integrity of the accelerated approval program, which is designed to bring safe and effective drugs to patients with unmet medical needs as quickly as possible,” Dr. Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

“The program allows the FDA to approve a drug or biologic product intended to treat a serious or life-threatening condition based on an outcome that can be measured earlier than survival that demonstrates a meaningful advantage over available therapies. However, when confirmatory trials do not confirm clinical benefit, a reevaluation must be performed to determine if the approval should be withdrawn.”

Since the program began in 1992, only 6% of accelerated approvals for cancer drugs have been withdrawn, according to the FDA.

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