Targeting Mutant IDH in Glioma: Mechanistic Insights and Clinical Implications of Vorasidenib

This systematic review was conducted to test the hypothesis that vorasidenib, a dual inhibitor of mutant IDH1 and IDH2 enzymes, improves clinical outcomes in patients with IDH-mutant low-grade gliomas (LGGs), particularly by prolonging progression-free survival (PFS), delaying the need for chemoradiotherapy, and maintaining an acceptable safety profile. The data were derived from nine clinical trials (Phase I–III) identified through a PRISMA-guided search of six major databases up to June 2025. These studies included both early-phase single-arm trials and randomized controlled trials, with sample sizes ranging from approximately 48 to 331 patients. The populations consisted mainly of adults with histologically confirmed IDH1- or IDH2-mutant gliomas, often with residual or recurrent, non-enhancing disease. Vorasidenib was administered orally at varying doses (25–300 mg/day), with later-phase trials commonly using 40–50 mg daily, and compared against placebo or alternative IDH inhibitors such as ivosidenib. Outcomes assessed included PFS, objective response rate (ORR), time to next intervention (TTNI), reduction in the oncometabolite 2-hydroxyglutarate (2-HG), and adverse events. Risk of bias was generally low, with seven studies rated as low risk and two showing some concerns related to randomization.
This dataset includes the PRISMA flowchart and supplementary checklist.