Regorafenib in Recurrent Glioblastoma Patients: A Large and Monocentric Real-Life Study

SIMPLE SUMMARY: In the last years, treatments for recurrent glioblastoma patients have shown limited efficacy in terms of OS. In the REGOMA trial, regorafenib demonstrated encouraging results in this setting of population. Indeed, in this randomized, phase 2 study the OS was significantly improved in the regorafenib arm compared with the standard lomustine treatment. Noteworthy, based on the REGOMA trial results, regorafenib was included in the NCCN 2021 guidelines as a preferred regimen for recurrent glioblastoma patients. To date, no studies have analyzed the impact of regorafenib in patients treated outside of clinical trials. We performed a large study in order to evaluate the safety and efficacy of regorafenib in the real-life population of recurrent GBM patients. Our results were superimposable to the ones reported in the REGOMA trial and regorafenib should be considered as an interesting drug in a population with a very poor prognosis and an unmet clinical need. ABSTRACT: Despite multimodal treatment with surgery and radiochemotherapy, the prognosis of glioblastoma remains poor, and practically all glioblastomas relapse. To date, no standard treatment exists for recurrent glioblastoma patients and traditional therapies have showed limited efficacy. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor showing encouraging benefits in recurrent GBM patients enrolled in the REGOMA trial. We performed a large study to investigate clinical outcomes and the safety of regorafenib in a real-life population of recurrent glioblastoma patients. Patients receiving regorafenib outside clinical trials at the Veneto Institute of Oncology were retrospectively reviewed. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, prior first line therapy according to “Stupp protocol”, Eastern Cooperative Oncology Group (ECOG) performance status score ≤1. According to the original schedule, patients received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle. The primary endpoints of the study were overall survival and safety. A total of 54 consecutive patients were enrolled. The median age was 56, MGMT methylated status was found in 28 out of 53 available patients (52.8%), IDH mutation in 5 (9.3%) and 22 patients were receiving steroids at baseline. The median overall survival was 10.2 months (95% CI, 6.4–13.9), the OS-12 was 43%. Age, MGMT methylation status and steroid use at baseline were not statistically significant on a multivariate analysis for OS. Patients reporting a disease control as best response to regorafenib demonstrated a significant longer survival (24.8 months vs. 6.2 months for patients with progressive disease, p = 0.0001). Grade 3 drug-related adverse events occurred in 10 patients (18%); 1 patient (2%) reported a grade 4 adverse event (rash maculo-papular). No death was considered to be drug-related. This study reported the first large “real-life” experience of regorafenib in recurrent glioblastoma. Overall, our results are close to the ones reported in the previous phase 2 study, despite the fact that we had a longer survival. We showed the encouraging activity and tolerability of this treatment in recurrent glioblastoma patients when used as a second-line treatment.