Trends in Efficacy Endpoints in Phase II Glioblastoma Trials: A Regulatory Science Analysis (FY2020–FY2022)

Background/Objectives: In glioblastoma trials, efficacy evaluation often deviates from the standard Response Evaluation Criteria in Solid Tumors (RECIST), an objective response rate (ORR) method, because of the unique nature of brain tumors. In phase II trials from the fiscal years (FYs) 2017–2019, primary endpoints (PEs) were overall survival (OS) at 29%, ORR at 20%, progression-free survival (PFS) at 17%, and OS rate at 10%. Clinical trial methodologies have likely evolved in recent years. This study analyzed trends in efficacy endpoint settings for phase II trials from FY2020 to FY2022 compared with FY2017–2019. Methods: Using Clarivate’s Cortellis™ Clinical Trial Intelligence database, 116 phase II glioblastoma trials initiated between April 2020 and March 2023 were identified. After exclusions, 88 trials were analyzed. Trial characteristics, PEs, secondary endpoints (SEs), and designs were summarized and compared to prior data. Results: Of 101 PEs in the 88 trials, approximately half targeted newly diagnosed patients, and most tested pharmaceutical products. The most common PEs were FS (22%), OS (20%), and PFS rate (17%), while among 299 SEs, OS (15%), PFS (15%), and quality of life (14%) were most frequent. Time-to-event outcomes were employed in 74 (73%) trials, whereas ORR was used as a PE in only 7 trials (8%). ORR as a PE was significantly lower than in FY2017–2019 (p = 0.022). Conclusions: Recent glioblastoma trials show increased diversity in efficacy endpoints with less reliance on ORR compared to earlier periods, reflecting evolving strategies to address the unique challenges of glioblastoma treatment and evaluation.