CNS

Ivosidenib in Isocitrate Dehydrogenase 1–Mutated Advanced Glioma

In the August 10, 2020 edition of Journal of Clinical Oncology, Ingo K. Mellinghoff and colleagues report on the results of the IDH1 inhibitor, ivosidenib in IDH1 mutated WHO grade 2 glioma.

PURPOSE

Because IDH 1 mutations occur in more than 74% of low-grade gliomas, investigators wanted to assess the utility of ivosidenib, an IDH1 inhibitor, in low-grade gliomas, substratified by MRI enhancement.

METHODS

The clinical trial was a multicenter, open-label, phase I, dose escalation and expansion study of the IDH 1 inhibitor, ivosidenib in patients with mutated IDH1 in patients with advanced gliomas.

RESULTS

In the study, 66 patients with advanced gliomas who were administered ivosidenib had no dose-limiting toxicities reported. The maximum tolerated dose was not reached; 500 mg once per day was utilized for the expansion cohort. The grade 3/4 adverse event rate was 19.7%; 3% (n = 2) which investigators considered to be treatment related. In patients who had MRI evidence of non-enhancing gliomas (n = 35), the objective response rate was 2.9%, with 1 partial response. 30 / 35 patients (85.7%) with non-enhancing gliomas achieved stable disease compared with 14 / 31 (45.2%) with enhancing glioma. Median PFS 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 non-enhancing and enhancing glioma cohorts, respectively.  After exploratory analysis was performed, ivosidenib was shown to reduce the volume and growth rates of nonenhancing tumors. The authors concluded “In 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.”

Reference:

Ivosidenib in Isocitrate Dehydrogenase 1–Mutated Advanced Glioma

https://ascopubs.org/doi/full/10.1200/JCO.19.03327

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