Major Points

• INDIGO was the first randomized, double-blind, placebo-controlled, phase 3 trial of a targeted IDH inhibitor in glioma, enrolling 331 patients at 77 centers across 10 countries.
• The trial uniquely targeted the watch-and-wait population — patients with residual/recurrent grade 2 IDH-mutant glioma after surgery who had not yet received radiation or chemotherapy.
• The primary endpoint was met with a dramatic 61% reduction in the risk of progression or death: median PFS 27.7 vs 11.1 months (HR 0.39; 95% CI 0.27-0.56; P<0.001).
• The key secondary endpoint — time to next intervention (RT, chemo, or surgery) — was even more striking: HR 0.26 (95% CI 0.15-0.43; P<0.001), meaning vorasidenib substantially delayed the need for more toxic therapies.
• At the data cutoff, imaging-based progression occurred in only 28.0% of the vorasidenib group vs 54.0% of the placebo group. No deaths occurred in either group at median follow-up of 14.2 months.
• The safety profile was manageable: grade >=3 AEs in 22.8% (vorasidenib) vs 13.5% (placebo). The main toxicity was elevated ALT (grade >=3 in 9.6% vs 0%), requiring liver function monitoring.
• The trial was unblinded early at the second prespecified interim analysis based on overwhelming efficacy, and patients in the placebo group were allowed to cross over to vorasidenib.
• INDIGO represents a paradigm shift in low-grade glioma management — offering a targeted, oral therapy during the watch-and-wait period that can delay or defer the neurotoxicity associated with radiation and chemotherapy.