Vorasidenib can improve outcomes in patients with low-grade IDH1/2-mutated gliomas, according to research presented at the ASCO Annual Meeting 2023.1
Vorasidenib significantly improved progression-free survival (PFS) and time-to-next intervention (TTNI), when compared to placebo, in the phase 3 INDIGO trial.
These results will likely change the standard practice for treating low-grade IDH1/2-mutated gliomas, said Rimas Vincas Lukas, MD, of Northwestern University in Evanston, Illinois, an ASCO discussant who was not involved in the INDIGO study.
However, that change will depend on whether vorasidenib is granted regulatory approval.
The INDIGO study (ClinicalTrials.gov Identifier: NCT04164901) enrolled patients who had IDH1/2-mutated, grade 2 oligodendroglioma or astrocytoma and had undergone surgery. Patients were 12 years of age or older at diagnosis, had measurable non-enhancing lesions at least 1 cm in diameter, and were not in need of immediate chemotherapy or radiotherapy.
A total of 331 patients were randomly assigned to receive vorasidenib (40 mg once daily in 28-day cycles; n=168) or placebo (n=163). Baseline characteristics were well balanced between the arms.
One patient assigned to the vorasidenib arm did not ultimately receive the drug, and 52 patients in the placebo arm crossed over to receive vorasidenib. The median follow-up was 14.0 months for the vorasidenib arm and 14.3 months for the placebo arm.
The median PFS was 27.7 months in the vorasidenib arm and 11.1 months in the placebo arm (hazard ratio, 0.39; 95% CI, 0.27-0.56; P =.000000067) .
The median TTNI was not reached in the vorasidenib arm and was 17.8 months in the placebo arm (hazard ratio, 0.26; 95% CI, 0.15-0.43; P=.000000019).
Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 22.8% of patients receiving vorasidenib and 13.5% of patients receiving placebo. The most common grade 3 or higher TEAEs in the vorasidenib arm were increased alanine aminotransferase (9.6%), increased aspartate aminotransferase (4.2%), and seizure (4.2%). There were no fatal TEAEs.
These results were also published in The New England Journal of Medicine.2
Disclosures: This research was supported by Servier. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. Mellinghoff IK, Van Den Bent MJ, Blumenthal DT, et al. INDIGO: A global, randomized, double-blinded, phase 3 study of vorasidenib versus placebo in patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. ASCO 2023. June 2-6, 2023. Abstract LBA1.
2. Mellinghoff IK, Van Den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. Published online June 4, 2023. doi:10.1056/NEJMoa2304194