Ivosidenib in Isocitrate Dehydrogenase 1–Mutated Advanced Glioma
| Autor: | Benjamin M. Ellingson, Katharine E. Yen, Sung Choe, Robert J. Young, Elizabeth A. Maher, Gregory M. Cote, Matthias Holdhoff, Patrick Y. Wen, Raymond Y. Huang, Bin Fan, Lori Steelman, Ingo K. Mellinghoff, Timothy F. Cloughesy, Macarena I. de la Fuente, Liewen Jiang, Shuchi Sumant Pandya, Min Lu, Chris Bowden, Filip Janku, Mehdi Touat, Howard A. Burris |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Extramural business.industry medicine.disease 03 medical and health sciences Tumor grade 030104 developmental biology 0302 clinical medicine Isocitrate dehydrogenase Oncology Multicenter study 030220 oncology & carcinogenesis Glioma medicine Cancer research business |
| Zdroj: | Journal of Clinical Oncology. 38:3398-3406 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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