KEY POINTS
- EORTC 22033-26033 was a randomized phase III intergroup trial involving 478 patients with clinically high-risk World Health Organization grade 2 glioma, with a median follow-up of approximately 13 years.
- Patients received radiotherapy to 50.4 Gy in 28 fractions or dose-dense temozolomide at 75 mg/m² daily on days 1–21 of each 28-day cycle, for up to 12 cycles.
- There was no significant difference in progression-free survival or overall survival between the two treatment groups. Tumor tissue was available for post hoc molecular classification in 351 patients (73%).
- In isocitrate dehydrogenase–mutant, non-codeleted astrocytoma, median overall survival was 6.6 years with radiotherapy versus 6.7 years with temozolomide (hazard ratio 0.98, 95% confidence interval 0.67–1.44; P = .93). In codeleted oligodendroglioma, median overall survival was 12.9 versus 14.9 years, respectively (hazard ratio 0.88, 95% confidence interval 0.52–1.49; P = .63).
- Among 64 patients with isocitrate dehydrogenase–wild-type tumors, median overall survival favored temozolomide: 4.7 versus 2.5 years with radiotherapy (hazard ratio 0.47, 95% confidence interval 0.27–0.82; P = .0068).
CLINICAL TAKEAWAY
The trial does not identify either radiotherapy or temozolomide monotherapy as the superior initial strategy for molecularly defined grade 2 astrocytoma or oligodendroglioma. These are mature randomized data, but molecular classification was performed post hoc in only 73% of patients, and the study did not evaluate the combined-modality regimens now used in practice, making the findings highly relevant rather than practice-changing.