Evaluating vorasidenib in the treatment of IDH1-mutant or IDH2-mutant low-grade gliomas

INTRODUCTION: Isocytrate dehydrogenase (IDH)-mutant astrocytomas and oligodendrogliomas are adult-type diffuse gliomas that disproportionately affect younger patients. Despite an often indolent initial course, these tumors remain incurable and commonly recur, with the potential for malignant progression. Vorasidenib is the first brain-penetrant, oral, dual inhibitor of mutant IDH1 and IDH2 shown to improve progression-free survival in patients with grade 2 IDH-mutant diffuse glioma. AREAS COVERED: This review examines the treatment landscape for low-grade glioma, vorasidenib's development, including its pharmacology, efficacy in the INDIGO trial, safety profile, and clinical role. It also addresses current evidence gaps and ongoing clinical trials with vorasidenib. EXPERT OPINION: Vorasidenib provides an active treatment alternative to surveillance for selected patients in whom radiotherapy and chemotherapy can be safely deferred. Its principal clinical role lies in delaying chemoradiotherapy and its associated acute and long-term toxicities while maintaining disease control. Key unanswered questions include its effect on overall survival, mechanisms of resistance, optimal treatment duration and sequencing, comparative effectiveness, and outcomes in real-world practice. Until further evidence emerges, use beyond non-enhancing, surgery-only grade 2 IDH-mutant glioma should generally be limited to clinical trials. Results from ongoing studies evaluating vorasidenib in broader disease settings and combination strategies are eagerly awaited.