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Open questions on vorasidenib

Antoine Seyve1, François Ducray1,2

  • 1Neuro-oncology department, Hospices Civils de Lyon.

Current Opinion in Oncology
|October 1, 2025
PubMed
Abstract

Insights

Vorasidenib shows promise for isocitrate dehydrogenase (IDH)-mutant gliomas, offering potential differentiation therapy and seizure control. Further research is needed to confirm long-term benefits and explore its use in higher-grade gliomas.

Area of Science:

  • Neuro-oncology
  • Molecular oncology
  • Clinical trials

Background:

  • Isocitrate dehydrogenase (IDH)-mutant gliomas are a distinct subtype of brain tumors.
  • Vorasidenib has shown efficacy in IDH-mutant grade 2 gliomas.
  • Current understanding of vorasidenib's long-term effects and optimal use is evolving.

Purpose of the Study:

  • To summarize open questions regarding vorasidenib's long-term benefit in IDH-mutant grade 2 gliomas.
  • To discuss the optimal use of vorasidenib in IDH-mutant grade 2 gliomas.
  • To explore the potential use of vorasidenib in IDH-mutant grade 3 and 4 gliomas.

Main Methods:

  • Review of updated results from the INDIGO trial.
  • Analysis of potential mechanisms of action, including differentiation therapy.
  • Consideration of advanced imaging techniques for response assessment (volumetric analysis, amino acid PET).

Main Results:

  • Vorasidenib may act as a differentiation therapy in IDH-mutant grade 2 gliomas.
  • Updated INDIGO trial results suggest additional benefits in seizure control.
  • Contrast-enhancement may be a better indicator for treatment response than histological grade, suggesting potential use in selected grade 3 gliomas.

Conclusions:

  • Vorasidenib is emerging as a first-line treatment for many IDH-mutant grade 2 gliomas.
  • Ongoing research aims to clarify its long-term impact on cognition, quality of life, and overall survival.
  • Further trials are investigating vorasidenib's role in other contexts, including maintenance therapy and combination treatments.
Keywords:
astrocytomagliomaisocitrate dehydrogenase 1isocitrate dehydrogenase 2oligodendrogliomavorasidenib

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