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Article Dans Une Revue Journal of Clinical Oncology Année : 2020

Ivosidenib in Isocitrate Dehydrogenase 1 – Mutated Advanced Glioma

Ingo K Mellinghoff
  • Fonction : Auteur
Benjamin M Ellingson
  • Fonction : Auteur
Elizabeth Maher
  • Fonction : Auteur
Macarena de la Fuente
  • Fonction : Auteur
Matthias Holdhoff
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Gregory M Cote
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Howard Burris
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Filip Janku
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Robert J Young
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Raymond Huang
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Liewen Jiang
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Sung Choe
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Bin Fan
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Katharine Yen
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Min Lu
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Chris Bowden
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Lori Steelman
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Shuchi Pandya
  • Fonction : Auteur
Timothy F Cloughesy
  • Fonction : Auteur
Patrick Y Wen
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Résumé

PURPOSE Diffuse gliomas are malignant brain tumors that include lower-grade gliomas (LGGs) and glioblastomas. Transformation of low-grade glioma into a higher tumor grade is typically associated with contrast enhancement on magnetic resonance imaging. Mutations in the isocitrate dehydrogenase 1 ( IDH1) gene occur in most LGGs (> 70%). Ivosidenib is an inhibitor of mutant IDH1 (mIDH1) under evaluation in patients with solid tumors. METHODS We conducted a multicenter, open-label, phase I, dose escalation and expansion study of ivosidenib in patients with m IDH1 solid tumors. Ivosidenib was administered orally daily in 28-day cycles. RESULTS In 66 patients with advanced gliomas, ivosidenib was well tolerated, with no dose-limiting toxicities reported. The maximum tolerated dose was not reached; 500 mg once per day was selected for the expansion cohort. The grade ≥ 3 adverse event rate was 19.7%; 3% (n = 2) were considered treatment related. In patients with nonenhancing glioma (n = 35), the objective response rate was 2.9%, with 1 partial response. Thirty of 35 patients (85.7%) with nonenhancing glioma achieved stable disease compared with 14 of 31 (45.2%) with enhancing glioma. Median progression-free survival was 13.6 months (95% CI, 9.2 to 33.2 months) and 1.4 months (95% CI, 1.0 to 1.9 months) for the nonenhancing and enhancing glioma cohorts, respectively. In an exploratory analysis, ivosidenib reduced the volume and growth rates of nonenhancing tumors. CONCLUSION In patients with m IDH1 advanced glioma, ivosidenib 500 mg once per day was associated with a favorable safety profile, prolonged disease control, and reduced growth of nonenhancing tumors.
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hal-04481741 , version 1 (28-02-2024)

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Ingo K Mellinghoff, Benjamin M Ellingson, Mehdi Touat, Elizabeth Maher, Macarena de la Fuente, et al.. Ivosidenib in Isocitrate Dehydrogenase 1 – Mutated Advanced Glioma. Journal of Clinical Oncology, 2020, 38 (29), pp.3398-3406. ⟨10.1200/JCO.19.03327⟩. ⟨hal-04481741⟩
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