Who will benefit from vorasidenib? Review of data from the literature and open questions

The clinical efficacy of isocitrate dehydrogenase (IDH) inhibitors in the treatment of patients with grade 2 IDH-mutant (mIDH) gliomas is a significant therapeutic advancement in neuro-oncology. It expands treatment options beyond traditional radiation therapy and cytotoxic chemotherapy, which may lead to significant long-term neurotoxic effects while extending patient survival. The INDIGO study demonstrated that vorasidenib, a pan-mIDH inhibitor, improved progression-free survival for patients with grade 2 mIDH gliomas following surgical resection or biopsy compared to placebo and was well tolerated. However, these encouraging results leave a wake of unanswered questions: Will higher-grade mIDH glioma patients benefit? When is the appropriate timing to start and stop treatment? Where does this new treatment option fit in with other treatment modalities? In this study, we review the limited data available to start addressing these questions, provide a framework of how to discuss these gaps with current patients, and highlight what is needed from the neuro-oncology community for more definitive answers.