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.

本系统综述旨在验证如下假说：沃拉塞尼布（vorasidenib）作为突变型IDH1与IDH2酶的双重抑制剂，可改善IDH突变型低级别胶质瘤（LGG）患者的临床结局，具体表现为延长无进展生存期（PFS）、推迟放化疗需求，并维持可接受的安全性。研究数据源自2025年6月前，通过PRISMA指南指导下的检索从6个主要数据库中筛选出的9项I-III期临床试验。这些研究涵盖早期单臂试验与随机对照试验，样本量跨度约为48至331例患者。研究人群主要为经组织学证实携带IDH1或IDH2突变的成人胶质瘤患者，多数存在残留或复发的非增强性病变。沃拉塞尼布以口服方式给药，剂量范围为25~300 mg/日，后期试验通常采用每日40~50 mg的剂量，并与安慰剂或其他IDH抑制剂（如艾伏尼布（ivosidenib））进行对照。本次研究评估的结局指标包括无进展生存期（PFS）、客观缓解率（ORR）、至下次干预时间（TTNI）、癌代谢物2-羟基戊二酸（2-HG）水平降幅以及不良事件。偏倚风险整体较低，其中7项研究被评为低偏倚风险，2项研究存在与随机化相关的潜在问题。本数据集包含PRISMA流程图与补充检查表。