Efficacy evaluation of anticancer agents in single-arm clinical trials: analysis of review reports from Pharmaceuticals and Medical Devices Agency

Background: Comparative studies often cannot be conducted for cancer types with a small patient population. We reviewed the efficacy evaluations of new drug approvals in Japan based on the results of single-arm clinical trials. Methods: We reviewed review reports on anticancer agents approved in Japan between 2006 and 2019 that are publicly available on the website of the Pharmaceuticals and Medical Devices Agency, Japan. Results: The number of single-arm trial-based approvals increased, with a total of 43 drugs approved during the study period. Compared with comparative trial-based approvals, single-arm trial-based approvals had a tendency toward more biomarker-related indications (37.2% vs 22.6%, p =.053), as well as more approvals for hematological malignancies, orphan designation, and response-related outcomes as the primary endpoint. Only 13 of the pivotal trials of single-arm trial-based approvals had a predefined threshold for efficacy based on the same target population as the pivotal trial, and nearly half of the trials did not have an appropriate predefined threshold for efficacy. In particular, the efficacy thresholds for clinical trials for 4 molecular targeted agents were set based on the results of the nonbiomarker-selected population. Conclusions: Evidence on standard cancer therapies for rare molecular subtypes is lacking. External control data from registries might support the efficacy evaluations of new drugs for newly established rare molecular subtypes.