A Study on the Description of Anticancer Drug Combination Therapy in the Package Insert in Japan

Background: Approved anticancer drug combinations are classified into the following groups: broader than (broad label), the same as (same label), or smaller than (narrow label) the series of combination regimens investigated in clinical studies. The present research attempted to elucidate the characteristics of the broad/narrow label to clarify what types of combination regimens are given these labels. Methods: All anticancer drugs approved in Japan between April 2006 and March 2020 and their review reports were selected from the Pharmaceuticals and Medical Devices Agency (PMDA) website. The differences in the number of regimens in clinical trials given each label were investigated using Tukey’s test. Multinomial logistic regression analysis was also conducted to examine the factors influencing each category. Results and Discussion: There were significant differences in the numbers of regimens among the labels. The factors that significantly contributed to labeling could not be identified. However, key features were identified. If there were multiple clinically comparable regimens and a clinical trial was conducted to evaluate the clinical benefit of adding new anticancer agents to one of the major regimens, there was a high probability of receiving a broad label. A narrow label may be granted if a regimen considered clinically comparable despite possessing a different mechanism of action does not exhibit clinical benefits in phase III studies. Conclusion: The present study revealed the PMDA stance for reviewing the clinical data of anticancer combination therapies submitted by sponsors in their totality to allow physicians to provide patient-centric, evidence-based, optimized cancer care to patients.