MRI Findings Show Vorasidenib More Than Doubles Progression-Free Survival in Patients with Grade 2 IDH Gliomas

Daily dosing with vorasidenib, an oral inhibitor of mutant isocitrate dehydrogenase (IDH)1 and IDH2 enzymes, may represent a significant advance in the management of patients with grade 2 IDH-mutant gliomas, according to magnetic resonance imaging (MRI) monitoring and other study findings presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

In new phase 3 trial research, also published recently in the New England Journal of Medicine, researchers compared the use of daily 40 mg dosing of vorasidenib in 28-day cycles to placebo in 331 patients 12 years of age or older who had residual or recurrent grade 2 IDH-mutant gliomas.1 The study authors noted that the vorasidenib group was comprised of 168 patients (median age of 40.5) and there were 163 patients (median age of 39) in the placebo group.

Utilizing brain MRI scans, researchers assessed progression-free survival, the time from initial randomization to first documentation of progressive disease or death, for 47 patients in the vorasidenib group and 88 patients in the placebo group, according to the study.

The researchers found the median imaging-based progression-free survival for patients treated with vorasidenib was 27.7 months in comparison to 11.1 months in the placebo group. Vorasidenib was also associated with a significantly longer duration of time prior to a subsequent intervention. According to the research, the likelihood of not needing a subsequent treatment intervention was 83.4 percent at 24 months in the vorasidenib group in comparison to 27 percent in the placebo group.1

“The results … showed that treatment with vorasidenib significantly improved both imaging-based progression-free survival according to blinded independent review and the time to the next intervention, as compared with placebo, among patients who were considered to be candidates for a watch-and-wait approach,” wrote lead study author Ingo K. Mellinghoff, M.D., F.A.C.P., chair of the Department of Neurology at Memorial Sloan Kettering Cancer Center in New York, N.Y., and colleagues.

For patients 12 years of age or older who had residual or recurrent grade 2 IDH-mutant gliomas, researchers found the median imaging-based progression-free survival for patients treated with vorasidenib was 27.7 months in comparison to 11.1 months in the placebo group.

(Editor’s note: For related content, see “Adjunctive AI Software for Brain MRI Gets FDA Clearance for Assessing High-Grade Gliomas,” “Can Abbreviated MRI Have an Impact in Neuroimaging?” and “FDA Clears AI-Powered MRI Software to Assess for Brain Atrophy.”)

While acknowledging that chemotherapy and radiation therapy are the standard of care for patients with IDH-mutant grade 2 gliomas deemed to be at high risk for early disease progression, the study authors maintained that monitoring with serial brain MRI scans is pursued instead of immediate adjunctive chemotherapy after diagnosis for “many patients with IDH-mutant grade 2 gliomas.”

Noting that adjuvant chemoradiotherapy has been linked to toxic effects such as neurocognitive dysfunction and citing a low incidence of serious adverse events with vorasidenib, the study authors said an improved watch-and-wait period in this high-risk population offers “an opportunity to detect a clear signal of anti-tumor activity” for emerging targeted treatments being studied in placebo-controlled research.

“Our study shows that targeting IDH mutations with vorasidenib significantly delays tumor growth and the need for more toxic therapies. This is clinically meaningful because patients diagnosed with grade 2 glioma with IDH mutations are typically young, otherwise healthy individuals,” said Dr. Mellinghoff in a statement from the Memorial Sloan Kettering Cancer Center.2 “The results of the phase III INDIGO trial offer a rare chance to change the treatment paradigm for this type of glioma and could bring the first new targeted therapy for diffuse low-grade glioma.”

References

1. Mellinghoff IK, van den Bent MJ, Blumenthal DT. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2304194. Published online June 4, 2023. Accessed June 4, 2023.

2. ASCO 2023: New research from Memorial Sloan Kettering Cancer Center identifies significant treatment advancement for brain tumors. Memorial Sloan Kettering Cancer Center. Available at: https://www.mskcc.org/news-releases/asco-2023-new-research-from-mskcc-identifies-significant-treatment-advancement-for-brain-tumors . Published June 4, 2023. Accessed June 4, 2023.