Ivosidenib in isocitrate dehydrogenase 1-mutated advanced glioma Journal Article

   


Authors: Mellinghoff, I. K.; Ellingson, B. M.; Touat, M.; Maher, E.; De La Fuente, M. I.; Holdhoff, M.; Cote, G. M.; Burris, H.; Janku, F.; Young, R. J.; Huang, R.; Jiang, L.; Choe, S.; Fan, B.; Yen, K.; Lu, M.; Bowden, C.; Steelman, L.; Pandya, S. S.; Cloughesy, T. F.; Wen, P. Y.
Article Title: Ivosidenib in isocitrate dehydrogenase 1-mutated advanced glioma
Abstract: PURPOSEDiffuse 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.METHODSWe conducted a multicenter, open-label, phase I, dose escalation and expansion study of ivosidenib in patients with mIDH1 solid tumors. Ivosidenib was administered orally daily in 28-day cycles.RESULTSIn 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.CONCLUSIONIn patients with mIDH1 advanced glioma, ivosidenib 500 mg once per day was associated with a favorable safety profile, prolonged disease control, and reduced growth of nonenhancing tumors.
Keywords: analysis; inhibitor; tumors; response assessment; myeloid-leukemia; low-grade glioma; abl tyrosine kinase; genomic; 2-hydroxyglutarate; oncometabolite; idh1 mutations; mutant idh2
Journal Title: Journal of Clinical Oncology
Volume: 38
Issue: 29
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2020-10-10
Start Page: 3398
End Page: 3406
Language: English
ACCESSION: WOS:000587957600001
DOI: 10.1200/jco.19.03327
PROVIDER: wos
PMCID: PMC7527160
PUBMED: 32530764
Notes: Article -- Source: Wos
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MSK Authors
  1. Ingo K Mellinghoff
    269 Mellinghoff
  2. Robert J Young
    228 Young
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