Prognostic impact of hand-foot skin reaction in regorafenib-treated adult-type diffuse gliomas: A multicenter Turkish Oncology Group study.

Glioblastoma, IDH-wildtype is the most aggressive primary brain tumor in adults, and treatment options for recurrent disease are limited. Regorafenib, an oral multikinase inhibitor, has shown efficacy in glioblastoma at first recurrence, but its role in later recurrences and in other adult-type diffuse gliomas remains unclear. This multicenter retrospective study aimed to evaluate the safety and efficacy of regorafenib and to identify prognostic factors in patients with adult-type diffuse gliomas, including glioblastoma, who were treated at the second or subsequent recurrences. A total of 68 patients from 22 institutions were analyzed. The median overall survival (OS) was 3.84 months, and the median progression-free survival was 2.46 months. The objective response rate was 13%, and the disease control rate was 48%. Adverse events occurred in 80.9% of patients, most commonly fatigue, anemia, and elevated transaminases. Hand-foot skin reaction (HFSR) of any grade was observed in 36.4% of patients and was associated with significantly improved OS (HR: 0.41; p = 0.005). Regorafenib demonstrated a manageable safety profile and modest activity in this heavily pretreated population. The development of HFSR emerged as a potential prognostic marker for treatment benefit. Taken together, our findings support further exploration of regorafenib in this setting and suggest that HFSR may serve as a practical marker to guide treatment continuation.