FDA Announces Oncologic Drugs Advisory Committee to Review 6 Indications Granted Accelerated Approval

The FDA announced in a statement that it will hold a public meeting of the Oncologic Drugs Advisory Committee from April 27 to 29 to address the indications granted accelerated approval for 6 therapies, following reports being released regarding results from confirmatory trials that did not verify clinical benefit.

The therapies to be discussed at the meeting treat patients with breast, urothelial, gastric, and hepatocellular cancers. These treatments include:

• Atezolizumab (Tecentriq, Genentech Inc) in combination with paclitaxel protein-bound to treat adult patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express programmed death-ligand 1 (PD-L1), as well as for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy.
• Pembrolizumab (Keytruda, Merck Sharpe & Dohme Corp) to treat patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy; patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 and with disease progression on or after 2 or more prior lines of therapy, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, human epidermal growth factor receptor 2/neu-targeted therapy; and the treatment of patients with hepatocellular carcinoma who previously received treatment with sorafenib.
• Nivolumab (Opdivo, Bristol Myers Squibb) given alone to treat patients with hepatocellular carcinoma who previously received treatment with sorafenib.

In the statement from the FDA, 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, explained that the FDA is committed to supporting the integrity of the accelerated approval program in order to bring safe and effective drugs to patients 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,” Pazdur said in a press release. “However, when confirmatory trials do not confirm clinical benefit, a reevaluation must be performed to determine if the approval should be withdrawn.”

The meeting had been requested by the FDA’s Oncology Center of Excellence due to the current, industry-wide focus on the evaluation of accelerated approvals of oncology therapies for which confirmatory trials have not yet confirmed clinical benefit.

Upon receiving the updates on the therapies provided at this meeting, the committee will discuss individual drugs more generally, addressing specifically the continued approval of the indication of the drug and whether additional trials are necessary.

From the current evaluation of accelerated approvals being conducted, 4 indications for oncology therapies have been withdrawn or have withdrawals planned due to consultation with the FDA:

1. Nivolumab to treat patients with metastatic small cell lung cancer with progression following platinum-based chemotherapy and at least 1 other line of therapy.
2. Durvalumab (Imfinzi, AstraZeneca) to treat patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
3. Pembrolizumab to treat patients with metastatic small cell lung cancer with disease progression on or following platinum-based chemotherapy and at least 1 other prior line of therapy.
4. Atezolizumab to treat patients with locally advanced or metastatic urothelial carcinoma 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.

The withdrawals of accelerated approvals based on consultations with the FDA are not a frequent occurrence, the statement noted, as only 6% of accelerated approvals for oncology indications have been withdrawn to date, including the 4 listed. However, efforts to discuss the approvals of indications with the FDA remain an important aspect of ensuring the integrity of the accelerated approval program.

“This public meeting of the advisory committee creates an opportunity for external oncology experts and patients with cancer to share input and perspective with the FDA.” Pazdur said in the press release. “After this advisory meeting, our staff will consider the committee’s comments and will make final decisions regarding continuing approval of each indication."

REFERENCE

US Food and Drug Administration. FDA In Brief: FDA Oncologic Drugs Advisory Committee to Review Status of Six Indications Granted Accelerated Approval. FDA website. https://www.fda.gov/news-events/fda-brief/fda-brief-fda-oncologic-drugs-advisory-committee-review-status-six-indications-granted-accelerated. Published March 11, 2021. Accessed March 12, 2021.