Dr Cloughesy on Extended Follow-Up Data for Vorasidenib in IDH1/2 Mutant Glioma

At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Timothy Cloughesy, MD, University of California, Los Angeles, presented updated results from the phase 3 INDIGO trial (NCT06809322). The extended analysis evaluates the long-term efficacy and safety of vorasidenib (Voranigo) compared with a placebo in patients with grade 2 mutant isocitrate dehydrogenase 1 or 2 (IDH1/2) glioma who have undergone surgery but do not yet require immediate chemoradiotherapy.

With a median follow-up of 41.6 months, the new data includes more than 3 years of follow-up and an additional 21.3 months of unblinded data collected after the trial's initial unblinding. Following unblinding, all 163 patients in the placebo group discontinued their assigned treatment, and 144 crossed over to receive vorasidenib.

The updated findings demonstrate that the clinical benefits of vorasidenib are durable and continue to improve over time:

• Progression-Free Survival (PFS): The median PFS for patients treated with vorasidenib reached 44.1 months.
• Time to Next Intervention (TTNI): The median TTNI for the vorasidenib group was not estimable, as only 23.8% of these patients required subsequent treatment, indicating a substantial delay in the need for more aggressive interventions.
• Objective Response Rate (ORR): The ORR rose to 20.8%, showing gradual and durable improvement with longer treatment, while an additional 72.6% of patients achieved stable disease.
• Seizure Reduction: Patients experienced a 72% reduction in the rate of on-treatment seizures.

The safety profile remained consistent with previous reports and was generally tolerable, consisting mostly of low-grade adverse events. Grade 3 or higher events included increased liver enzymes (ALT at 10.8% and AST at 4.8%) and seizures (4.8%). Fewer than 5% of patients discontinued treatment due to adverse events, and no treatment-related deaths occurred. Experts note these findings underscore how long-term IDH inhibition can successfully delay disease progression for a patient population that historically relied on a "watch and wait" approach.