Top Line: Regorafenib, an oral multikinase inhibitor with antiangiogenic activity, earned an NCCN listing for recurrent GBM after improving survival (7.4 v 5.6 months) compared to lomustine in the small, phase 2 REGOMA trial.
The Study: The catch, though, was that REGOMA's lomustine arm performed below expectation with baseline imbalances in age, steroid use, MGMT status, and time to progression all favoring regorafenib. GBM AGILE was a Bayesian adaptive platform trial that sought to evaluate regorafenib’s efficacy for newly diagnosed and recurrent GBM. It enrolled 335 patients, 28% with newly diagnosed MGMT-unmethylated GBM, and 72% with recurrent GBM. In the new GBM group, they were randomized to receive chemoradiation followed by either adjuvant TMZ or adjuvant regorafenib. In the recurrent group, they were randomized to lomustine or regorafenib. Regorafenib did not significantly improve OS in the newly diagnosed group (14.3 v 14.6 months) or the recurrent group (9.2 v 9.7 months). Importantly, the GBM AGILE control arm with recurrent disease performed in line with historical norms, suggesting the prior REGOMA's control was the outlier, not its regorafenib arm. Adverse effects were higher with regorafenib, particularly in those with newly diagnosed disease where the rate of grade 3-4 AEs hit 74%.
TBL: Regorafenib did not improve survival in newly diagnosed unmethylated GBM or recurrent GBM in the randomized GBM AGILE trial. | Wen, J Clin Oncol 2026
The Study: The catch, though, was that REGOMA's lomustine arm performed below expectation with baseline imbalances in age, steroid use, MGMT status, and time to progression all favoring regorafenib. GBM AGILE was a Bayesian adaptive platform trial that sought to evaluate regorafenib’s efficacy for newly diagnosed and recurrent GBM. It enrolled 335 patients, 28% with newly diagnosed MGMT-unmethylated GBM, and 72% with recurrent GBM. In the new GBM group, they were randomized to receive chemoradiation followed by either adjuvant TMZ or adjuvant regorafenib. In the recurrent group, they were randomized to lomustine or regorafenib. Regorafenib did not significantly improve OS in the newly diagnosed group (14.3 v 14.6 months) or the recurrent group (9.2 v 9.7 months). Importantly, the GBM AGILE control arm with recurrent disease performed in line with historical norms, suggesting the prior REGOMA's control was the outlier, not its regorafenib arm. Adverse effects were higher with regorafenib, particularly in those with newly diagnosed disease where the rate of grade 3-4 AEs hit 74%.
TBL: Regorafenib did not improve survival in newly diagnosed unmethylated GBM or recurrent GBM in the randomized GBM AGILE trial. | Wen, J Clin Oncol 2026