A dual inhibitor of the mutant IDH1 and IDH2 enzymes, vorasidenib significantly improved progression-free survival and delayed the time to the next intervention In patients with grade 2 IDH-mutant glioma, a study shows. “Although the current trial showed the single-agent activity of vorasidenib in patients with previously untreated WHO grade 2 glioma, additional trials will be necessary to define the role of vorasidenib, alone or as part of combination-therapy regimens, in patients with glioma who have received cancer therapy previously or who present with WHO grade 3 or 4 disease,” the authors conclude.
In a double-blind, phase 3 trial, patients with treatment-naive (other than surgery) residual or recurrent grade 2 IDH-mutant glioma were randomized to oral vorasidenib 40 mg once daily or matched placebo in 28-day cycles. Based on a primary endpoint of imaging-based progression-free survival, the study showed: “A total of 331 patients were assigned to receive vorasidenib (168 patients) or placebo (163 patients). At a median follow-up of 14.2 months, 226 patients (68.3%) were continuing to receive vorasidenib or placebo. Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival, 27.7 months vs. 11.1 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.27 to 0.56; P <0.001). The time to the next intervention was significantly improved in the vorasidenib group as compared with the placebo group (hazard ratio, 0.26; 95% CI, 0.15 to 0.43; P <0.001). Adverse events of grade 3 or higher occurred in 22.8% of the patients who received vorasidenib and in 13.5% of those who received placebo. An increased alanine aminotransferase level of grade 3 or higher occurred in 9.6% of the patients who received vorasidenib and in no patients who received placebo.”