Ctni-64. Phase 2 Study of Regorafenib in Bevacizumab-Refractory Recurrent Glioblastoma

PURPOSE This phase 2 non-randomized prospective study was conducted to evaluate the efficacy and safety of regorafenib monotherapy in bevacizumab-refractory recurrent glioblastoma (GBM). METHODS Patients were enrolled based on documented radiographic progression of histologically confirmed GBM following second- or third-line bevacizumab therapy. Patients received oral regorafenib monotherapy at a target dose of 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 (RANO) criteria. Patients continued treatment with regorafenib therapy until they experienced progression or dose-limiting toxicity. RESULTS Based on the analysis of 13 patients (median age 66 years, KPS ≥70), 12 of 13 (92%) had progressive disease (PD) on brain MRI; 1 patient went off study due to Grade 3 weakness prior to first assessment, 3-month progression-free survival (PFS-3) was 7.7% with median (95% CI) PFS of 1.0 (0.4 - 1.8) months. Overall survival (OS) was 38% at 6 months and 23% at 12 months, with median (95% CI) OS 4.1 (2.0 - 7.3) months. Grade 3 or 4 adverse events were fatigue (31%), muscle weakness (23%), and 7% (n=1) each for pancreatitis, palmar-plantar erythrodysesthesia syndrome, and thromboembolic event. There were no Grade 5 adverse events. CONCLUSION Regorafenib did not improve overall or progression-free survival in bevacizumab-refractory recurrent glioblastoma.