Clinical Trial Evidence Supporting US Food and Drug Administration Approval of Novel Cancer Therapies Between 2000 and 2016

Question What are the available data on cancer treatment outcomes for new cancer therapies approved by the US Food and Drug Administration? Findings In this comparative effectiveness study of 92 novel cancer therapies approved for 100 indications over 17 years, 44% of drug approvals were based on data from nonrandomized clinical trials. Randomized clinical trials typically reported that these drugs were associated with substantial tumor responses and delays in the time to progression or death, but the median absolute increase in overall survival was only 2 months. Meaning This study's findings indicate that, at the time of drug approval, limited supporting data are available to decision-makers, and the increase in overall survival associated with new cancer drugs is typically small. Importance Clinical trial evidence used to support drug approval is typically the only information on benefits and harms that patients and clinicians can use for decision-making when novel cancer therapies become available. Various evaluations have raised concern about the uncertainty surrounding these data, and a systematic investigation of the available information on treatment outcomes for cancer drugs approved by the US Food and Drug Administration (FDA) is warranted. Objective To describe the clinical trial data available on treatment outcomes at the time of FDA approval of all novel cancer drugs approved for the first time between 2000 and 2016. Design, Setting, and Participants This comparative effectiveness study analyzed randomized clinical trials and single-arm clinical trials of novel drugs approved for the first time to treat any type of cancer. Approval packages were obtained from drugs@FDA, a publicly available database containing information on drug and biologic products approved for human use in the US. Data from January 2000 to December 2016 were included in this study. Main Outcomes and Measures Regulatory and clinical trial characteristics were described. For randomized clinical trials, summary treatment outcomes for overall survival, progression-free survival, and tumor response across all therapies were calculated, and median absolute survival increases were estimated. Tumor types and regulatory characteristics were assessed separately. Results Between 2000 and 2016, 92 novel cancer drugs were approved by the FDA for 100 indications based on data from 127 clinical trials. The 127 clinical trials included a median of 191 participants (interquartile range [IQR], 106-448 participants). Overall, 65 clinical trials (51.2%) were randomized, and 95 clinical trials (74.8%) were open label. Of 100 indications, 44 indications underwent accelerated approval, 42 indications were for hematological cancers, and 58 indications were for solid tumors. Novel drugs had mean hazard ratios of 0.77 (95% CI, 0.73-0.81; I-2 = 46%) for overall survival and 0.52 (95% CI, 0.47-0.57; I-2 = 88%) for progression-free survival. The median tumor response, expressed as relative risk, was 2.37 (95% CI, 2.00-2.80; I-2 = 91%). The median absolute survival benefit was 2.40 months (IQR, 1.25-3.89 months). Conclusions and Relevance In this study, data available at the time of FDA drug approval indicated that novel cancer therapies were associated with substantial tumor responses but with prolonging median overall survival by only 2.40 months. Approval data from 17 years of clinical trials suggested that patients and clinicians typically had limited information available regarding the benefits of novel cancer treatments at market entry. This comparative effectiveness research examines clinical trial data on treatment outcomes used to support US Food and Drug Administration approval of novel cancer therapies that were approved for the first time between 2000 and 2016.