Characteristics of Trials and Regulatory Pathways Leading to US Approval of Innovative vs. Non-Innovative Oncology Drugs

First-generation oncology drugs and most second-generation variants across four drug classes (BCR-ABL TKIs, ALK+ TKIs, CD20 monoclonal antibodies, and HER2 monoclonal antibodies) were approved through expedited pathways and predominantly based on single-arm trials, with second-generation drugs showing similar approval patterns to their first-generation counterparts. While expedited approval facilitates earlier patient access, this regulatory approach is associated with increased risk of post-approval safety-related labeling changes and unanticipated adverse events.