Phase 2 study of regorafenib in patients with progressive glioblastoma after failure of bevacizumab

Background: Treatment options in progressive glioblastoma (GBM) are limited, especially in patients who have experienced disease progression while receiving bevacizumab therapy. This phase 2 study was conducted to evaluate the efficacy and safety of regorafenib monotherapy in patients with GBM. Methods: Eligible patients had radiographic progression of histologically confirmed GBM following second- or third-line bevacizumab therapy. They received regorafenib monotherapy using the dose escalation strategy demonstrated in the ReDOS phase 2 clinical trial evaluating regorafenib in metastatic colon cancer. The target dose was 160 mg once daily, administered for 3 weeks on/1 week off in 28-day cycles. Patients underwent brain magnetic resonance imaging (MRI) every 8 weeks and were assessed via modified Response Assessment in Neuro-Oncology criteria. Patients continued treatment with regorafenib therapy until they experienced progression or excessive toxicity. Results: Based on the analysis of 13 enrolled patients, there were no responses and 12 of 13 (92.3%) had progressive disease on brain MRI; 1 patient went off study due to an adverse event occurring before assessment. The median overall survival (OS) was 4.1 months (95% CI 2.0-7.3). The OS at 12 months was 23% (0.2-46). The PFS at both 3 and 6 months was 7.7% (0.0-22.2%) with a median PFS of 1.0 month, (0.4-1.8). There was a total of 14 Grade 3 or 4 AEs and no Grade 5 AEs. Conclusions: Regorafenib did not improve OS or PFS in bevacizumab-refractory recurrent glioblastoma. The study was halted early due to futility. Trial Registration: NCT04051606.