Accelerated Approval in Oncology: FDA Touts Successes, Responds to Criticism

Regulatory NewsRegulatory News | 05 March 2018 |  By 

A majority of oncology treatments granted accelerated approval over the last 25 years have gone on to demonstrate a clinical benefit, US Food and Drug Administration (FDA) officials write in a review published in JAMA Oncology last week.

But the review notes that 5% of those drugs were eventually withdrawn from the market and that drugmakers have not yet completed postmarketing requirements (PMRs) for 40% of those indications.


Unlike regular approval, accelerated approval requires a drug to show an effect on a surrogate endpoint that is "reasonably likely to predict clinical benefit" for patients with a serious condition where there is an unmet medical need. When granting accelerated approval FDA will also require the sponsor to complete PMRs to confirm the product's benefit.

Since the creation of the program in 1992 through 31 May 2017, FDA has granted accelerated approval to 64 products for malignant hematology and oncology indications for a total of 93 new indications compared to 174 oncology indications granted full approval during that time. Some drugs have been granted accelerated approval for multiple indications, such as Merck's Keytruda (pembrolizumab) and Novartis' Gleevec (imatinib), each of which has been granted accelerated approval for six indications.


So far, FDA says the PMRs for 51 (55%) of those indications were fulfilled in a median 3.4 years after gaining accelerated approval. Of the remaining 42 indications, 37 (40%) had not completed their PMR studies, and 5 (5%) were pulled from the market by their sponsors.

Four of the five withdrawn drugs were done so voluntarily after confirmatory trials failed to verify clinical benefit. The remaining drug, Roche's Avastin (bevacizumab), had its indication for HER2-negative breast cancer withdrawn in 2011 following a decision by former FDA Commissioner Margaret Hamburg.

The review also found that most of the indications granted accelerated approvals were studied in single-arm studies (72%) for their initial accelerated approvals, and the most common endpoints for those studies were response rate (87%) or time-to-end points such as profession-free survival or time to progression (9%).

For the drugs with completed PMRs, the review found progression-free survival and time to progression to be the most common study endpoint (39%). Overall survival was the endpoint for 29% of the PMR studies, followed by response rate for 26% of the studies.

Based on these findings, FDA says the accelerated approval program has proven to be successful in bringing new therapies to patients more quickly.

"The [accelerated approval] AA program balances uncertainty associated with smaller sample sizes and earlier clinical trial end points with providing faster access to promising agents for those with serious or life-threatening disease," the authors write.

The authors also address criticism that confirmatory studies for oncology drugs granted accelerated approval should focus on overall survival or quality of life endpoints.

"For multiple reasons, the feasibility of OS or health-related quality of life as primary end points can be problematic," the authors write.

In a series of posts on Twitter, Vinay Prasad, a hematologist-oncologist and assistant professor of medicine at the Oregon Health Sciences University, leveled criticisms at the review, citing his earlier research finding low correlation between progression-free survival and overall survival in metastatic cancers.

JAMA Oncology


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