FDA to Reassess 6 Oncology Immunotherapy Indications Granted Accelerated Approval

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The FDA will reassess 6 indications for immune checkpoint inhibitors that were granted accelerated approval but failed to prove clinical benefit in confirmatory trials.

The FDA will reassess 6 indications for immune checkpoint inhibitors that were granted accelerated approval but failed to prove clinical benefit in confirmatory trials in a public meeting of the Oncologic Drugs Advisory Committee on April 27-29. The discussion will cover drugs being used to treat patients with breast, urothelial, gastric, and hepatocellular cancers.

Initiated by the FDA’s Oncology Center of Excellence, the hearings will allow external experts and patients to provide their insight on the treatments before FDA staff makes final decisions on the continued approval of the indications in question.

The indications up for discussion, which involve 3 drugs, include:

  • Atezolizumab (Tecentriq) in combination with nab-paclitaxel (Abraxane) for the treatment of patients with PD-L1–positive unresectable locally advanced or metastatic triple-negative breast cancer (TNBC)
  • Atezolizumab as monotherapy for patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy
  • Pembrolizumab (Keytruda) as monotherapy for patients with locally advanced or mUC who are not eligible for cisplatin-containing chemotherapy
  • Pembrolizumab for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma that express PD-L1 and has progressed after 2 or more prior lines of therapy
  • Pembrolizumab for patients with hepatocellular carcinoma (HCC) previously treated with sorafenib
  • Nivolumab (Opdivo) as a single agent for patients with HCC who previously received sorafenib

The meeting was announced after several voluntary drug indication withdrawals by pharmaceutical companies and is part of an industry-wide evaluation of accelerated approvals in oncology that saw confirmatory trials fail, according to the FDA.

In addition to the 6 aforementioned indications up for discussion, 4 others have either already been voluntarily withdrawn or are going to be voluntarily withdrawn following pharmaceutical companies’ discussions with the FDA:

  • Nivolumab for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy
  • Durvalumab (Imfinzi) for the treatment of patients with locally advanced or mUC whose disease has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy
  • Pembrolizumab for the treatment of patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy, and
  • Atezolizumab for treatment of patients with locally advanced or mUC who have disease progression during or following platinum-containing atezolizumab chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

These withdrawals and the impending assessments put a spotlight on the FDA’s accelerated approval program, which allows drugs to gain indications based on a surrogate end point. This facilitates quick approval and makes drugs available to patients while pharmaceutical companies conduct the required confirmatory trials to prove clinical benefit and earn regular approval for the indication.

“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. 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,” Richard Pazdur, MD, 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 statement. “However, when confirmatory trials do not confirm clinical benefit, a reevaluation must be performed to determine if the approval should be withdrawn.”

Although the accelerated approvals provide patients with potentially life-changing drugs more quickly than the traditional approval pathway, the subsequent withdrawals may create a complicated landscape for stakeholders, from payers to physicians and patients.

Joseph Alvarnas, MD, editor-in-chief of Evidence-Based Oncology™, a publication of The American Journal of Managed Care® (AJMC®), gave his take on the implications for patients and payers in a video interview with AJMC® after news of the upcoming meeting broke.

And when it comes to the current situation, Alvarnas only anticipates similar actions going forward. When you set up a system to streamline the adoption of the newest agents, it is inevitable that there will be at least some that require reevaluation.

Just 6% of the oncology indications under the accelerated approval program, including the 4 recent voluntary withdrawals, have been withdrawn, according to the FDA briefing. Alvarnas admitted that he is not surprised at the current initiative and expects more drug reassessments down the line.

He said, “One of the challenges is that as you set up a system to enhance the throughput of new agents—and I strongly favor that, because I think for patients and families who need access, getting speed to access is really important, especially in the cancer domain—the ability to dial back based upon further aggregated data is an essential function of a system which also imparts greater speed.”

Reference

FDA in brief: FDA Oncologic Drugs Advisory Committee to review status of six indications granted accelerated approval. FDA. March 11, 2021. Accessed March 12, 2021. https://www.fda.gov/news-events/fda-brief/fda-brief-fda-oncologic-drugs-advisory-committee-review-status-six-indications-granted-accelerated