Verifying clinical benefit of new anticancer drugs after regulatory approval based on exploratory studies

Background : In Japan, anticancer drugs are often approved based on the Objective Response Rate (ORR) when the conduct of a confirmatory study is difficult or expected to take a considerably long time. However, it remains unclear how frequently post-marketing confirmatory studies are conducted and for which indications they are implemented. We aimed to understand the status of post-marketing confirmatory studies for approved anticancer drugs. Methods : We investigated the status of post-marketing confirmatory studies on anticancer drug indications approved based on ORR in Japan between 2015 and 2022. Results : We found that 60% of the indications did not have planned confirmatory studies, with many receiving “orphan drug” designations. This observation is consistent with the Japanese regulations thatallow the approval of anticancer drugs based on the ORR, for which confirmatory studies are difficult to conduct or expected to take a long time. Post-marketing confirmatory studies were less commonly requested from the regulatory authority in Japan than in the US. Although the results of post-marketing confirmatory studies were often utilized in regulatory actions in Japan (including modifications to approved indications), no indications were found where these results led to withdrawal of approval or additional confirmatory study requirements, and the evaluations of the results were not disclosed when they did not lead to regulatory actions. Conclusions : To enhance transparency in the regulatory review process and facilitate smoother regulatory actions based on the results of post-marketing confirmatory studies, it may be beneficial to require the submission of the results of postmarketingconfirmatory studies if it is feasible following the approval based on ORR.