Exploring Seizure Reduction in INDIGO: Signals, Limitations, and Clinical Interpretation

For patients with IDH-mutant diffuse glioma, seizure control remains one of the most meaningful clinical outcomes beyond radiographic tumor stability. Although tumor-directed therapies are often assessed through progression-free survival and imaging-based endpoints, seizure burden can have a major impact on function, independence, and overall quality of life, making it an increasingly important part of the treatment conversation.

At the 2026 AAN Annual Meeting in Chicago, Katherine B. Peters, MD, PhD, neuro-oncologist at Duke Health and professor of neurology and neurosurgery at the Preston Robert Tisch Brain Tumor Center, spoke with NeurologyLive® about the phase 3 INDIGO trial (NCT04164901), which evaluated vorasidenib in patients with IDH-mutant diffuse glioma. In addition to the trial’s established efficacy findings, Peters discussed emerging analyses that examined seizure-related outcomes in greater depth, offering perspective on how these data fit into the broader clinical picture. Her discussion also emphasized the importance of understanding both the strengths and the constraints of exploratory analyses when applying these results to patient care.

In this episode, Peters focuses on the seizure outcomes observed in INDIGO, including the numerical differences seen between vorasidenib and placebo among patients who experienced seizures during the study. She also reviews key limitations of the analysis, such as enrollment criteria requiring relatively controlled seizures and reliance on patient-reported seizure diaries, while explaining how reductions in tumor volume may help contextualize the seizure findings and support a biologically plausible treatment effect.