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

Macarena I de la Fuente; Mehdi Touat; Martin J van den Bent; Matthias Preusser; Katherine B Peters; Robert J Young; Raymond Y Huang; Benjamin M Ellingson; David Capper; Joanna J Phillips; Lia M Halasz; Helen A Shih; Roberta Rudà; Mary Jane Lim-Fat; Deborah T Blumenthal; Michael Weller; Yoshiki Arakawa; James R Whittle; François Ducray; David A Reardon; Wenya Linda Bi; Giuseppe Minniti; Rifaquat Rahman; Shawn Hervey-Jumper; Susan M Chang; Patrick Y Wen

doi:10.1093/neuonc/noae259

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

Neuro Oncol. 2025 Jun 21;27(5):1135-1148. doi: 10.1093/neuonc/noae259.

Authors

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 (available on 2025-12-25)
DOI: 10.1093/neuonc/noae259

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.

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Publication types

Review

MeSH terms

Antineoplastic Agents* / therapeutic use
Brain Neoplasms* / drug therapy
Brain Neoplasms* / genetics
Glioma* / drug therapy
Glioma* / genetics
Glioma* / pathology
Humans
Isocitrate Dehydrogenase* / antagonists & inhibitors
Isocitrate Dehydrogenase* / genetics
Mutation*
Pyrimidines* / therapeutic use
Triazines* / therapeutic use

Substances

Isocitrate Dehydrogenase
Triazines
Antineoplastic Agents
Pyrimidines

Abstract

Publication types

MeSH terms

Substances

Grants and funding