Inside INDIGO: Updated Trial Insights and Clinical Implications

EP: 1.Redefining Gliomas Through Molecular Classification

EP: 2.Treatment Workflow for IDH-Mutant Gliomas

EP: 3.Integrating Molecular Markers Into Glioma Treatment Planning

EP: 4.Postsurgical Assessment and Early Management Considerations for IDH-Mutant Gliomas

Now Viewing

EP: 5.Inside INDIGO: Updated Trial Insights and Clinical Implications

EP: 6.Beyond the Trial: Treatment Considerations and Sequencing for IDH-Mutant Gliomas

Content above is prompted by the following:

The INDIGO trial represents a landmark randomized, placebo-controlled study evaluating vorasidenib (an IDH inhibitor) vs placebo in patients with progressive or persistent WHO grade 2 IDH-mutant gliomas. The study was designed with planned interim analyses for potential FDA approval, and during one such analysis, the results proved so compelling that the FDA recommended early study termination. The dramatic improvement in progression-free survival and time to next treatment intervention led to full FDA approval in August 2024, marking a significant milestone in glioma treatment.

The trial's success demonstrates the efficacy of targeted molecular therapy in IDH-mutant gliomas, offering a new treatment paradigm that addresses the infiltrative nature of these tumors. Unlike traditional radiation and chemotherapy, IDH inhibitors can theoretically reach microscopic disease throughout the brain via systemic circulation. The favorable safety profile of vorasidenib contrasts sharply with the potential short and long-term toxicities associated with radiation and chemotherapy, making it an attractive option for the typically young patient population.

Treatment sequencing discussions now include IDH inhibitors as a potential first-line option, though overall survival data remain immature given the long natural history of these tumors. Clinicians must balance patient preferences between daily oral therapy for extended periods vs intensive but time-limited radiation/chemotherapy regimens. The availability of IDH inhibitors allows for deferral of more toxic treatments while maintaining disease control, though careful counseling ensures patients understand that radiation and chemotherapy remain effective options for future use. This sequential approach maximizes treatment options while prioritizing quality of life in this young patient population with excellent long-term prognosis.