Unproven OS benefits from surrogate endpoint-based cancer drug approvals

Oct 28 2015

By Shreeya Nanda, Senior medwireNews Reporter

The majority of cancer drugs recently approved by the US Food and Drug Administration (FDA) on the basis of a surrogate endpoint either have an unknown effect on overall survival (OS) or have failed to show a survival benefit, say the authors of a research letter.

“Our results show that most cancer drug approvals have not been shown to, or do not, improve clinically relevant end points”, say Chul Kim (National Cancer Institute, Bethesda, Maryland, USA) and Vinay Prasad (Oregon Health and Sciences University, Portland, USA).

Between 2008 and 2012, the FDA approved 54 agents for the treatment of various malignancies. Of these, 36 (67%) were approved on the basis of a surrogate efficacy measure, such as progression-free or disease-free survival (47%) or response rate (53%), as indicated by a reduction in tumour size or volume.

A total of 15 drugs were approved via the accelerated regulatory pathway, and of note, all were based on a surrogate endpoint. By contrast, just over half (54%) of the agents approved via the traditional route were based on a surrogate measure for efficacy.

A systematic review of published literature showed that since approval and with a median follow-up of 4.4 years, treatment with just five of the 36 drugs (one of 15 fast-track and four of 21 traditional approvals) has led to an improvement in OS in randomised trials.

Eighteen agents have failed to prolong survival (six of 15 accelerated and 12 of 21 traditional approvals).

And for the remaining 13 drugs, the OS effects remain unknown, “meaning they remain untested or they have no reported survival results as primary or secondary outcome”, explain the authors.

Kim and Prasad write in JAMA Internal Medicine: “Since 2008, the FDA has approved a higher percentage of drugs than previously, and cancer drugs are approved on the basis of surrogates that have poor correlations with overall survival.

“Our results suggest that the FDA may be approving many costly, toxic drugs that do not improve overall survival”, they say, urging the crucial importance of enforcing postmarketing studies.

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