In the INDIGO trial, 85.6% of patients on vorasidenib were alive and free of further treatment at 18 months. On placebo the figure was 47.4%. That gap is the core of an approval the US Food and Drug Administration announced in early August 2024, as reported on August 6, for Voranigo, the brand name of vorasidenib.
The drug is cleared for patients aged 12 and older who have had surgery for a grade 2 astrocytoma or oligodendroglioma carrying a susceptible IDH1 or IDH2 mutation. It is, in the words of the coverage, the first systemic therapy approved for that group.
The trial numbers
INDIGO was an international, double-blind, placebo-controlled study of 331 patients. Everyone had a confirmed IDH mutation, a recurrent or residual tumor and a Karnofsky performance status of at least 80. Participants took either 40 mg of vorasidenib by mouth once a day or a placebo, until the disease progressed or side effects became unacceptable. Those on placebo could switch to vorasidenib once imaging documented progression.
The primary endpoint was progression-free survival judged by imaging. The hazard ratio came in at 0.39 (95% CI, 0.27-0.56; P <.0001) in favor of vorasidenib. For time to next intervention, the median was not reached with vorasidenib against 17.8 months on placebo (HR, 0.26; 95% CI, 0.15-0.43; P <.0001).
At 24 months, 83.4% of vorasidenib patients had avoided further treatment, against 27.0% on placebo. Only 11.3% of the vorasidenib group went on to another anticancer therapy. In the placebo group it was 35.6%.
The median age was 40.5 years in the vorasidenib arm and 39 in the placebo arm. Most participants were men with frontal tumors, and oligodendroglioma was the commonest type in both groups.
Side effects and dosing
Reactions in at least 15% of patients included headache, fatigue, musculoskeletal pain, COVID-19 infection, nausea, diarrhea and seizure. Serious (grade 3 or higher) toxicities involved raised liver enzymes and lower neutrophil counts. Laboratory abnormalities seen in at least 2% of patients also included elevated gamma-glutamyl transpeptidase.
Adults take 40 mg daily. Adolescents of 12 and older follow a weight rule: 40 mg for those weighing at least 40 kg, and 20 mg for those under 40 kg.
Sources
- FDA Approves Vorasidenib in IDH+ Astrocytoma/Oligodendroglioma (CancerNetwork)
- FDA Approves Vorasidenib for Grade 2 Astrocytoma, Oligodendroglioma With IDH1, IDH2 Mutations (Oncology Nursing News)
