Sixty-seven percent of cancer drugs that received FDA marketing approval from 2008 through 2012 were approved on the basis of a surrogate endpoint, according to findings from a research letter published in JAMA Internal Medicine.
Chul Kim, MD, MPH, clinical fellow in the medical oncology branch of the NCI, and Vinay Prasad, MD, MPH, assistant professor of medicine at Oregon Health Sciences University, found that 86% of these drugs approved based on surrogate endpoints had unknown effects on OS or had failed to show an OS improvement after several years of follow-up.
“A 2009 Government Accountability Office report criticized the U.S. FDA for failing to enforce postmarketing study commitments for surrogate approvals,” Kim and Prasad wrote. “Among the more than 400 postmarketing studies requested, approximately 30% were pending, ongoing, delayed or terminated years later, yet the FDA never exercised its authority to remove a product from the market. For these reasons, we sought to investigate how often cancer drugs are approved based on a surrogate endpoint, whether subsequent studies for these drugs are reported, and whether the drugs improve OS.”
Overall, the FDA approved 54 cancer drugs between 2008 and 2012. Of these, 36 were approved based on surrogate endpoints. Fifteen drugs received accelerated approval, all of which were based on surrogate endpoints. Surrogate endpoints also formed the basis of 21 of 39 traditional approvals.
Rate of response (53%) served as the most commonly used surrogate endpoint, followed by PFS or DFS (47%).
After a median follow-up of 4.4 years, only five drugs approved on the basis of a surrogate endpoint were shown through randomized clinical trials to improve OS. Eighteen drugs (50%) failed to improve OS, and 13 (36.1%) have unknown OS effects.
“Our results show that most cancer drug approvals have not been shown to, or do not, improve clinically relevant endpoints,” Kim and Prasad wrote.
Crossover occurred during the trials for 11 of 36 (31%) drugs. However, there was no difference in crossover between trials that found a survival benefit and those that did not (1 of 5 [20%] vs 10 of 18 [55%]).
“Our results suggest that the FDA may be approving many costly, toxic drugs that do not improve OS,” Kim and Prasad wrote. “Enforcement of postmarketing studies is therefore of critical importance.” – by Anthony SanFilippo
Disclosure: Kim and Prasad report no relevant financial disclosures.