Real-World Clinical Oncology Outcomes Associated with the Accelerated Approval Pathway

The accelerated approval (AA) pathway expedites treatment access for patients with unmet medical needs. However, evidence on the program's impact is lacking. This study assessed real-world clinical outcomes for AA drugs in solid tumor cancers. A nationwide electronic health record (EHR)-derived deidentified database was utilized to explore the impact of the AA pathway in patients with selected solid tumors from 2011 to 2023. Included patients received AA or non-AA products with the same indication. Outcomes were real-world progression-free survival (rwPFS) and overall survival (OS). Population-level health impacts were estimated via market share and real-world progression-free life years (rwPFLYs) and life years (LYs). Twenty-three AA indications were studied. At study completion, 83% of indications had their clinical benefit verified, whereas 17% had been withdrawn from the market. Overall, 78% of indications demonstrated significant improvements in rwPFS or OS, whereas none reported significantly worse rwPFS versus controls. In total, 44% and 48% of indications had >30% rwPFS and OS improvement, respectively. More indications with sample sizes >100 in the AA cohort demonstrated significant rwPFS gains [80% (12/15)] versus cohorts <100 [38% (3/8)]. An estimated 118,107 patients received AA drugs during their AA window, resulting in 56,399 rwPFLYs and 50,848 LYs gained. Most solid tumor AA indications were associated with improved clinical outcomes, providing substantial US population-level health gains. This EHR analysis provides insight into whether the AA pathway appropriately targets promising beneficial therapies. Expanding beyond randomized controlled trial evidence and conventional primary endpoints may be necessary to verify clinical benefit, particularly in rare tumors.

This study (the first examining the real-world outcomes associated with the AA period) found improved clinical outcomes for most AA drugs studied compared with existing treatments in solid tumor cancers. The improvements observed suggest potential health improvements at the US population level and the possibility of the need to look beyond randomized controlled evidence and traditional primary endpoints to verify the clinical benefit of AA drugs for relatively rare conditions.