Temozolomide Versus Radiotherapy as First-Line Therapy for Low-Grade Glioma: Mature Results of a Randomized Phase III Trial (EORTC 22033-26033/NCIC-CTG/TROG/MRC-CTU).

In 30 seconds

This multicenter, randomized phase III trial compared first-line radiotherapy with dose-dense temozolomide in 478 patients with clinically high-risk WHO grade 2 low-grade glioma. Overall, the assigned treatment did not significantly affect progression-free or overall survival. In post hoc molecular subgroups, survival was similar between treatments for IDH-mutant astrocytoma and oligodendroglioma. Among 64 patients with IDH-wild-type tumors, overall survival favored temozolomide: 4.7 versus 2.5 years (HR, 0.47 [0.27-0.82], P = .0068).

Key findings

• There was no significant difference in progression-free or overall survival between the randomized treatment arms.
• For IDH-mutant, 1p/19q-noncodeleted astrocytoma, median overall survival was 6.6-6.7 years irrespective of treatment arm (P = .93).
• For IDH-mutant, 1p/19q-codeleted oligodendroglioma, median overall survival was 12.9 years with radiotherapy and 14.9 years with temozolomide (HR, 0.88 [0.52-1.49], P = .63).
• In tumors without IDH mutations, overall survival was 4.7 years with temozolomide versus 2.5 years with radiotherapy (HR, 0.47 [0.27-0.82], P = .0068).

Why it matters

The findings show that molecular subtype is important when interpreting outcomes in low-grade glioma and comparing initial treatment approaches. The overall trial result does not establish a survival advantage for either single-modality treatment, while the subgroup result in IDH-wild-type tumors may inform further evaluation of treatment strategies. The authors also report that age alone may not retain its prognostic meaning after molecular classification.

What to keep in mind

Molecular reclassification was post hoc and based on analyzable tissue from 73% (351/478) of patients. The trial compared single-modality treatments; combined-modality therapy was not tested.