Abstract
BACKGROUND: Phase I oncology trials are often regarded as a therapeutic option for patients. However, such claims have relied on surrogate measures of benefit, such as objective response. METHODS: Using a systematic search of publications, we assessed the therapeutic value of phase I cancer trial participation by determining the probability that patients will receive active doses of treatments that eventually receive FDA approval or a National Comprehensive Cancer Network (NCCN) guideline recommendation for their indication. ClinicalTrials.gov, PubMed, American Society of Clinical Oncology reports, NCCN guidelines, and Drugs@FDA were searched between May 1, 2018, and July 31, 2018. All statistical tests were 2-sided. RESULTS: A total of 1000 phase I oncology trials initiated between 2005 and 2010 and enrolling 32 582 patients were randomly sampled from 3229 eligible trials on ClinicalTrials.gov. A total of 386 (1.2%) patients received a treatment that was approved by the US Food and Drug Administration for their malignancy at a dose delivered in the trial; including NCCN guideline recommendations, the number and proportion are 1168 (3.6%). Meta-regression showed a statistically significantly greater proportion of patients receiving a drug that was ultimately FDA approved in biomarker trials (rate ratio = 4.49, 95% confidence interval [CI] = 1.53 to 13.23; P = .006) and single-indication trials (rate ratio = 3.32, 95% CI = 1.21 to 9.15; P = .02); proportions were statistically significantly lower for combination vs monotherapy trials (rate ratio = 0.09, 95% CI = 0.01 to 0.68; P = .02). CONCLUSIONS: One in 83 patients in phase I cancer trials received a treatment that was approved for their indication at the doses received. Given published estimates of serious adverse event rates of 10%-19%, this represents low therapeutic value for phase I trial participation.