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Original Investigation
May 28, 2019

An Overview of Cancer Drugs Approved by the US Food and Drug Administration Based on the Surrogate End Point of Response Rate

Author Affiliations
  • 1Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland
  • 2Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland
JAMA Intern Med. 2019;179(7):915-921. doi:10.1001/jamainternmed.2019.0583
Key Points

Question  When the US Food and Drug Administration approves cancer drugs based on response rate (RR) (ie, the percentage of patients whose cancer shrinks beyond an arbitrary threshold), what is the RR?

Findings  In this review of 85 cancer drug indications approved on the basis of RR, the median RR was 41%. Of the 85 approvals, 14 (16%) had RR less than 20%, 28 (33%) had an RR less than 30%, and 40 (47%) had an RR less than 40%.

Meaning  Many cancer drugs are approved on the basis of low or modest RRs, typically in single-arm studies.


Importance  Approximately one-third of cancer drugs are approved based on response rate (RR)—the percentage of patients whose tumors shrink beyond an arbitrary threshold—typically assessed in a single-arm study.

Objective  To characterize RR end points used by the US Food and Drug Administration (FDA) for cancer drug approval.

Design, Setting, and Participants  A retrospective review of FDA-approved drug indications in oncology from 2006 to 2018.

Exposures  Data related to cancer type, line of therapy (first-line, second-line, or third-or-later-line treatment for advanced/metastatic disease), type of FDA approval pathway, trial design, sample size, and level of innovation were extracted.

Main Outcomes and Measures  The primary outcome was the RR used as the basis for FDA approval. The secondary outcome was rate of complete response.

Results  Eighty-five indications for 59 cancer drugs were identified, 32 (38%) received regular approval, and 53 (62%) were granted accelerated approval. Twenty-nine (55%) accelerated approvals were later converted to regular approval. Of these, 6 (21%) approvals showed overall survival benefit, 16 (55%) later established progression-free survival benefit, and 7 (24%) continued to use RR but gained regular approval. The median RR among the 85 indications was 41% (interquartile range [IQR], 27%-58%). Among them, 14 of 85 (16%) had an RR less than 20%, 28 of 85 (33%) had an RR less than 30%, and 40 of 85 (47%) had an RR less than 40%. The median complete RR for 81 participants was 6% (IQR, 2%-22%). The median sample size among studies leading to approval was 117 (IQR, 76-182; range, 18-1052 participants). Drugs with accelerated approval pending confirmatory data had lower RR compared with drugs that have completed most postmarketing efficacy requirements (median, 28%; IQR, 15%-50% vs median, 42%; IQR, 31%-58%; P = .02).

Conclusions and Relevance  Many cancer drugs approved on the basis of response rate offer numerically low or modest response rates. Most premarket studies accrue more than 100 patients. Some of these drugs could potentially be tested in premarket randomized clinical trials measuring directly end points that demonstrate clinical benefit.

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