Temozolomide Added to Radiation Significantly Improves Long-Term Survival in IDH-Mutant and 1p/19q-Codeleted Grade 2 Gliomas
Results From the Phase 3 ECOG-ACRIN E3F05 Trial
Results From the Phase 3 ECOG-ACRIN E3F05 Trial
Key Clinical Takeaways
- Design/Population: In an updated molecular analysis of the phase 3 ECOG-ACRIN E3F05 trial, 172 patients with grade 2 gliomas received radiation therapy either alone or in combination with temozolomide. All tumors underwent 1p/19q co-deletion analysis by FISH, and 97 patients (56.3%) with sufficient tumor content (≥60%) underwent DNA methylation profiling using the Heidelberg Classifier v12 and Bethesda Classifier 2.0 to confirm IDH and 1p/19q status.
- Key Outcomes: At a median follow-up of 130 months, the addition of temozolomide improved OS in IDH-mutant, non-codeleted tumors (HR, 0.15), increasing 10-year OS from 39% to 80%. In 1p/19q-codeleted tumors, the addition of temozolomide improved OS (HR, 0.51), with 10-year OS increasing from 68% to 90%.
- Clinical Relevance: The combination of temozolomide and radiation therapy significantly improved long-term OS in both IDH-mutant, non-codeleted and 1p/19q-codeleted grade 2 gliomas, reinforcing combined chemoradiotherapy as a standard-of-care approach for molecularly defined lower-grade gliomas.
Updated molecular analyses from the phase 3 ECOG-ACRIN E3F05 trial demonstrated that the addition of temozolomide to radiation therapy significantly improved overall survival (OS) among patients with grade 2 gliomas.
These results were presented by David Schiff, MD, University of Virginia, Charlottesville, Virginia, at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting in Honolulu, Hawaii.
In this study, researchers analyzed formalin-fixed, paraffin-embedded (FFPE) tumor samples from 172 patients who received radiation either alone or in combination with temozolomide. Tumor specimens were evaluated for 1p/19q co-deletions using fluorescence in situ hybridization (FISH) following standard methods. A total of 97 patients had sufficient tumor content (≥60%) for DNA methylation profiling using the Heidelberg Classifier v12 and Bethesda Classifier 2.0 to refine molecular classification and confirm 1p/19q status. The primary endpoint was OS, analyzed by molecular subgroup.
At a median follow-up of 130 months, among the 172 patients, 74 demonstrated 1p/19q co-deletion by FISH, 38 were IDH-mutant, non-codeleted, 14 were IDH–wild-type, and 46 were non-codeleted with unknown IDH status (including 4 originally classified as 1p/19q undetermined). The addition of temozolomide improved OS in patients with IDH-mutant, non-codeleted tumors (hazard ratio [HR], 0.15) with 10-year OS increasing from 39% to 80%. The addition of temozolomide also improved OS in patients with codeleted tumors (HR, 0.51), increasing 10-year OS from 68% to 90%.
As Dr Schiff concluded, “The addition of temozolomide to radiation improves overall survival in both co-deleted and IDH-mutant, non-codeleted grade 2 gliomas.”
Source:
Schiff D, O’Neill A, Brown P, et al. Molecular analysis of outcomes in ECOG-ACRIN E3F05: Phase III study of radiation therapy with or without temozolomide for symptomatic or progressive low-grade gliomas. Presented at the SNO Annual Meeting. November 19 - 23, 2025; Honolulu, Hawaii. Abstract CTNI-29
