Proportion of patients in phase 2 oncology trials receiving treatments that are ultimately approved

Abstract

Background Many patients enroll in phase 1 dose expansion cohorts or phase 2 clinical trials (together referred to below as “phase 2”) seeking access to novel treatments. Little is known about the extent to which they benefit by enrolling. Herein, we use a novel metric of benefit—therapeutic proportion—to assess the probability that patients in phase 2 trials receive treatment that eventually advances to FDA (Food and Drug Administration) approval for their condition. Methods We randomly sampled 400 trials identified in a search of Clinicaltrials.gov for cancer phase 2 trials initiated between November 1, 2012 and November 1, 2015. We determined whether the drug/dose/indication tested in each trial advanced to FDA approval within 7.5 years. We determined whether the drug/dose/indication presented substantial clinical benefit using the ESMO-MCBS (European Society for Medical Oncology - Magnitude of Clinical Benefit Scale), or whether it received off-label recommendation in NCCN (National Comprehensive Cancer Network) guidelines. Results Collectively, trials in our sample enrolled 25 002 patient-participants in 608 specific treatment cohorts. A total of 4045 patients received a treatment that advanced to FDA approval (16.2%; 95% CI = 10.3 to 22.7). The therapeutic proportion increased to 19.4% (95% CI = 14.1 to 25.8) when considering NCCN off-label recommendations and decreased to 9.3% (95% CI = 4.7 to 14.6) for FDA-approved regimens considered being of substantial clinical benefit by ESMO-MCBS. Bootstrap test of mean difference showed no statistical difference in proportions based on drug class, trial phase, or sponsorship. Conclusion One in 6 patients in phase 2 clinical trials receives treatments that are eventually approved. This represents a higher therapeutic value than phase 1 trials.