Review

. 2025 Jun 21;27(5):1135-1148.

doi: 10.1093/neuonc/noae259.

The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma

Macarena I de la Fuente^{1

2}, Mehdi Touat^{3

4}, Martin J van den Bent^{3

4}, Matthias Preusser⁵, Katherine B Peters⁶, Robert J Young⁷, Raymond Y Huang⁸, Benjamin M Ellingson⁹, David Capper^{10

11}, Joanna J Phillips^{12

13}, Lia M Halasz¹⁴, Helen A Shih¹⁵, Roberta Rudà¹⁶, Mary Jane Lim-Fat¹⁷, Deborah T Blumenthal¹⁸, Michael Weller¹⁹, Yoshiki Arakawa²⁰, James R Whittle^{21

22

23}, François Ducray²⁴, David A Reardon²⁵, Wenya Linda Bi²⁶, Giuseppe Minniti^{27

28}, Rifaquat Rahman²⁹, Shawn Hervey-Jumper^{30

12}, Susan M Chang³¹, Patrick Y Wen²⁵

Affiliations

¹ Department of Neurology, University of Miami, Miami, Florida, USA.
² Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA.
³ Service de Neuro-oncologie, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, Paris Brain Institute, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, France.
⁴ Department of Neurology, Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
⁵ Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
⁶ Department of Neurosurgery, Preston Robert Tisch Brain Tumor Center, Duke University, Durham, North Carolina, USA.
⁷ Service Neuroradiology, Department of Radiology, Memorial Sloan Kettering Cancer, New York, New York, USA.
⁸ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁹ UCLA Brain Tumor Imaging Laboratory, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
¹⁰ German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Berlin, Heidelberg, Germany.
¹¹ Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹² Department of Pathology, University of California San Francisco, San Francisco, California, USA.
¹³ Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
¹⁴ Department of Radiation Oncology, University of Washington/Fred Hutchinson Cancer Center, Seattle, Washington, USA.
¹⁵ Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹⁶ Division of Neuro-Oncology, Department of Neuroscience, University of Turin, Turin, Italy.
¹⁷ Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁸ Neuro-Oncology, Tel Aviv Medical Center, Tel-Aviv University, Tel-Aviv, Israel.
¹⁹ Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
²⁰ Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
²¹ Department of Medical Biology, University of Melbourne, Parkville, Australia.
²² Personalised Oncology Division, WEHI, Parkville, Australia.
²³ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
²⁴ Department of Neuro-Oncology, East Group Hospital, Hospices Civils de Lyon, Université de Lyon, Université Claude Bernard, Lyon, France.
²⁵ Center For Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
²⁶ Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
²⁷ IRCCS Neuromed, Pozzilli, Isernia, Italy.
²⁸ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.
²⁹ Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³⁰ Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
³¹ Division of Neuro-Oncology, Department of Neurosurgery, University of California, San Francisco, California, USA.

PMID: 39723472
PMCID: PMC12187374
DOI: 10.1093/neuonc/noae259

Review

The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma

Macarena I de la Fuente et al. Neuro Oncol. 2025.

. 2025 Jun 21;27(5):1135-1148.

doi: 10.1093/neuonc/noae259.

Authors

Affiliations

¹ Department of Neurology, University of Miami, Miami, Florida, USA.
² Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA.
³ Service de Neuro-oncologie, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, Paris Brain Institute, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, France.
⁴ Department of Neurology, Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
⁵ Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
⁶ Department of Neurosurgery, Preston Robert Tisch Brain Tumor Center, Duke University, Durham, North Carolina, USA.
⁷ Service Neuroradiology, Department of Radiology, Memorial Sloan Kettering Cancer, New York, New York, USA.
⁸ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁹ UCLA Brain Tumor Imaging Laboratory, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
¹⁰ German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Berlin, Heidelberg, Germany.
¹¹ Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹² Department of Pathology, University of California San Francisco, San Francisco, California, USA.
¹³ Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
¹⁴ Department of Radiation Oncology, University of Washington/Fred Hutchinson Cancer Center, Seattle, Washington, USA.
¹⁵ Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹⁶ Division of Neuro-Oncology, Department of Neuroscience, University of Turin, Turin, Italy.
¹⁷ Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹⁸ Neuro-Oncology, Tel Aviv Medical Center, Tel-Aviv University, Tel-Aviv, Israel.
¹⁹ Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
²⁰ Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
²¹ Department of Medical Biology, University of Melbourne, Parkville, Australia.
²² Personalised Oncology Division, WEHI, Parkville, Australia.
²³ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
²⁴ Department of Neuro-Oncology, East Group Hospital, Hospices Civils de Lyon, Université de Lyon, Université Claude Bernard, Lyon, France.
²⁵ Center For Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
²⁶ Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
²⁷ IRCCS Neuromed, Pozzilli, Isernia, Italy.
²⁸ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.
²⁹ Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³⁰ Department of Neurological Surgery, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
³¹ Division of Neuro-Oncology, Department of Neurosurgery, University of California, San Francisco, California, USA.

PMID: 39723472
PMCID: PMC12187374
DOI: 10.1093/neuonc/noae259

Erratum in

Corrigendum to: The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.
[No authors listed] [No authors listed] Neuro Oncol. 2025 Feb 19:noaf032. doi: 10.1093/neuonc/noaf032. Online ahead of print. Neuro Oncol. 2025. PMID: 39970273 No abstract available.

Abstract

Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence. Consequently, there is an urgent need for innovative strategies that delay progression and the use of radiation therapy and chemotherapy. The recent Federal Drug Administration (FDA) approval of vorasidenib, a brain-penetrant small molecule targeting mutant IDH1/2 proteins, heralds a shift in the therapeutic landscape for IDH-mutant gliomas. In this review, we address the role of vorasidenib in the treatment of IDH-mutant gliomas, providing a roadmap for its incorporation into daily practice. We discuss ongoing clinical trials with vorasidenib and other IDH inhibitors, as single-agent or in combination with other therapies, as well as current challenges and future directions.

© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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Conflict of interest statement

M.I.D.: advisory board/consultant: Anheart, Fore, Rigel, and Servier. Honoraria for role as speaker: MedScape. M.T.: grant from Sanofy. Consulting fee from Servier, Novocure, Resilience, and NH TherAguix. Honoraria for lectures/educational events from Servier, Novocure, and Ono. Advisory board: Servier and Novocure. M.J.B.: honoraria for consultancy from Anheart Therapeutics, Boehringer Ingelheim, Fore Biotherapeutics, Genenta, Incyte, Mundipharm, Chimerix, Roche, and Servier and support for travel to meetings by Servier. M.P.: honoraria for lectures, consultation, or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, Medscape, and OncLive. K.B.P.: advisory board: Anheart, Blue Earth Diagnostics, NuVox Pharma, Ono Pharmaceutical Rigel, Sapience, Servier, and Telix. Research support: Biomimetix, Novocure, NuVox Pharma, Ono Pharmaceutical, Sapience, Servier, and Varian. R.J.Y.: consulting fees from Guerbet, NordicNeuroImaging, Olea Medical, Servier, Turing Medical, ICON plc, and RadMD, all unrelated to current work. R.Y.H.: consulting: Bristol Myers Squibb, Servier, Nuvation Bio. Scientific advisory: Vysioneer. B.M.E.: Alpheus Medical, Inc.–paid consultant, Ad Board. Carthera–data monitoring board. Chimerix Inc–consultant. Ellipses Pharma–paid consultant, Ad Board. Erasca–paid consultant . Global Coalition for Adaptive Research (GCAR)– paid consultant, Ad Board. Imaging Endpoints–paid consultant. Medicenna–paid consultant, Ad Board. Voiant–paid consultant, Ad Board. Monteris–paid consultant, Ad Board. Neosoma–paid consultant, Ad Board. Orbus Therapeutics–paid consultant, Ad Board. Sagimet Biosciences–paid consultant, Ad Board. Sapience Therapeutics–paid consultant. Servier Pharmaceuticals–paid consultant, Ad Board. Siemens–research grant. SonALAsense–paid consultant, Ad Board. Sumitomo Dainippon Pharma Oncology–consultant, Ad Board. Telix–consultant, Ad Board. Third Rock Ventures–consultant, Ad Board. D.C.: cofounder and shareholder of Heidelberg Epignostix GmbH. Royalties for IDH1 R132H mutation-specific antibody from DIANOVA GmbH. Research Funding from NOVOCURE. J.J.P.: nothing to disclose. LMH: Biomimetix, clinical trial funding. Kazia Therapeutics, clinical trial funding. UpToDate, royalties and consulting fees. HAS: AbbVie–research funding to the institution. Advanced Accelerator Applications-advisory board. Servier Pharmaceuticals–advisory board. UpToDate–honorarium for roles as editor, writer. MedLink Neurology–honorarium for role as a writer. R. Rudà: Receipt of grants/research supports: Bayer. Receipt of honoraria or consultation fees: Novocure, Servier, CureVac, and Genenta. M.J.L.-F.: grants or contracts from Brain Cancer Canada. Consulting fees from Cancer Care Ontario. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Servier and Novocure. Leadership role, SNO Board of Directors (unpaid). D.T.B.: nothing to disclose. M.W.: research grants from Novartis, Quercis, and Versameb, and honoraria for lectures or advisory board participation or consulting from Anheart, Bayer, Curevac, Medac, Neurosense, Novartis, Novocure, Orbus, Pfizer, Philogen, Roche, and Servier. Y.A.: grants from Philips, Otsuka, Chugai, Nihon Medi-Physics, Daiichi Sankyo, Stryker, Eisai, Japan Blood Products Organization, Ono Pharmaceutical, Taiho Pharma, Sumitomo Dainippon Pharma, Astellas Pharma, Incyte Biosciences, Servier, and personal fees from Nippon Kayaku, Novocure, UCB Japan, Ono Pharmaceutical, Brainlab, Merck, Chugai, Eisai, Daiichi Sankyo, Carl Zeiss, Nihon Medi-Physics, and Stryker. J.R.W.: research funding from AnHeart Therapeutics to institute; received consulting fees from AnHeart Therapeutics and Servier; being on advisory boards for Roche and Merck; is a data safety monitoring member for Telix Pharmaceuticals; as an employee of The Walter and Eliza Hall Institute may be eligible for milestone and royalty payments related to venetoclax. F.D.: scientific advisor or has served on advisory boards for the following companies: Novocure and Servier. D.A.R.: nothing to disclose. W.L.B.: nothing to disclose. G.M.: honoraria from Brainlab, Accuray Inc., Novocure Inc., and Servier. R.R.: advisory board consulting with Servier and Telix Pharmaceuticals; consulting with NH TherAguix; outside of submitted work. S.H.-J.: grant funding- NINDS, NCI, Curci Foundation, Robert Wood Johnson Foundation, and Servier Foundation. S.M.C.: nothing to disclose. P.Y.W.: research Support: Astra Zeneca, Black Diamond, Bristol Meyers Squibb, Chimerix, Eli Lily, Erasca, Global Coalition For Adaptive Research, Kazia, MediciNova, Merck, Novartis, Quadriga, Servier, and VBI Vaccines. Advisory Board/consultant: Anheart, Astra Zeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Glaxo Smith Kline, Kintara, Merck, Mundipharma, Novartis, Novocure, Prelude Therapeutics, Sagimet, Sapience, Servier, Symbio, Tango, Telix, and VBI Vaccines.

Figures

**Figure 1.**
Proposed incorporation of vorasidenib in the management algorithm based on INDIGO data and Federal Drug Administration (FDA) label. *FDA approval also includes patients with WHO grade 2 gliomas who have had a gross total resection (GTR). The discrepancy between the FDA label and the INDIGO criteria might be justified by the difficulty in assessing residual disease after surgery and the presence of microscopic infiltrative disease beyond imaging abnormalities in virtually all glioma patients. Indication for this population may vary depending on countries. **As assessed by the physician, no consensus on “high-risk” criteria.

See this image and copyright information in PMC

References

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The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma

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The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma

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