March 19, 2021
3 min read
FDA’s Oncologic Drugs Advisory Committee plans to hold a public meeting April 27-29 to review six indications for cancer drugs granted accelerated approval that subsequently failed to show clinical benefit in confirmatory trials.
The meeting is part of an industrywide reassessment of such cases, according to an FDA press release.
“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,” Richard Pazdur, MD, director of 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 the 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trials do not confirm clinical benefit, a reevaluation must be performed to determine if the approval should be withdrawn.”
‘Trying to strike a balance’
The industrywide reevaluation already has led to the voluntary withdrawal of indications by Bristol Myers Squibb and AstraZeneca, as well as plans for voluntary withdrawals by Merck and Genentech, according to FDA.
“All in all, accelerated approval is the FDA’s way of trying to strike a balance between expediting new drugs to patients with serious or life-threatening conditions vs. the potential for harm or lack of clinical benefit,” Marjorie Zettler, PhD, MPH, researcher and co-author of a 2018 paper that examined accelerated approvals of oncology drug indications and subsequent failed confirmatory trials, said in an interview with Healio. “So, when we know that the drug is not going to help the patients, the right thing to do is to pull it from the market. And that’s what FDA is doing.”
The four indications voluntarily withdrawn or slated to be withdrawn since December are:
- nivolumab (Opdivo, Bristol Myers Squibb) for patients with metastatic small cell lung cancer who experience disease progression after platinum-based chemotherapy and at least one other therapy;
- durvalumab (Imfinzi, AstraZeneca) for patients with locally advanced or metastatic urothelial carcinoma who experience progression during or after platinum-based chemotherapy or within a year of neoadjuvant or adjuvant platinum-containing chemotherapy;
- pembrolizumab (Keytruda, Merck) for patients with metastatic small cell lung cancer with progression on or following platinum-based chemotherapy and at least one other previous line of therapy; and
- atezolizumab (Tecentriq, Genentech) for patients with locally advanced or metastatic urothelial carcinoma who experience progression during or after platinum-containing chemotherapy or within a year of neoadjuvant or adjuvant platinum-containing chemotherapy.
Six additional indications for atezolizumab, pembrolizumab and nivolumab will be discussed at the upcoming meeting.
The atezolizumab indications relate to the use of the anti-PD-L1 agent in conjunction with paclitaxel protein-bound (Abraxane, Bristol Myers Squibb) for treatment of adults with unresectable, locally advanced or metastatic, PD-L1-positive triple-negative breast cancer, as well as for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy.
Pembrolizumab indications to be reviewed will include use of the anti-PD-1 antibody by patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy; patients with recurrent, locally advanced or metastatic, PD-L1-positive gastric or gastroesophageal junction adenocarcinoma who experience disease progression on or after two or more previous lines of therapy; and patients with hepatocellular carcinoma previously treated with sorafenib (Nexavar, Bayer).
Nivolumab indications to be discussed include the PD-1 inhibitor’s use as a single agent by patients with hepatocellular carcinoma previously treated with sorafenib.
‘A positive’ for patients, providers
The FDA introduced the accelerated pathway in 1992 to streamline the approval of HIV drugs. Currently, Zettler said, most accelerated approvals are for oncology indications.
Updates provided at the meeting will form the basis of a general discussion of individual drugs, and the committee will consider whether specific indications should retain approval or would require additional trials.
“This evaluation the FDA is conducting is a positive for both patients and for health care providers,” Zettler said. “Withdrawal of the drugs from the market or reevaluation of the clinical evidence, as FDA plans to do at the upcoming advisory committee meeting, is how the accelerated approval pathway was supposed to work. It doesn’t represent a failure of the program; it’s an appropriate action on the part of the FDA.”
FDA. FDA Oncologic Drugs Advisory Committee to review status of six indications granted accelerated approval. Available at: www.fda.gov/news-events/fda-brief/fda-brief-fda-oncologic-drugs-advisory-committee-review-status-six-indications-granted-accelerated. Accessed March 18, 2021.
Zettler M, et al. JAMA Oncol. 2018; doi:10.1001/jamaoncol.2018.0610.
For more information:
Marjorie Zettler, PhD, MPH, can be reached at [email protected]