Temozolomide chemotherapy versus radiotherapy in molecularly characterized (1p loss) low-grade glioma: A randomized phase III intergroup study by the EORTC/NCIC-CTG/TROG/MRC-CTU (EORTC 22033-26033).

Abstract

2007 Background: Outcome of low-grade glioma (LGG) is highly variable. We investigated whether primary chemotherapy in comparison to standard radiotherapy (RT) prolongs progression-free (PFS) and overall survival (OS), and whether prognostic molecular factors could be defined. Methods: Progressive, symptomatic or high-risk patients with a LGG requiring treatment other than surgery were randomized (after stratification for 1p-status) to either conformal RT (50.4 Gy/28 fractions) or dose-dense temozolomide [TMZ] (75 mg/m² daily x 21 days, q28 days, max. 12 cycles). Primary endpoint was PFS, secondary analyses included OS and impact of 1p status. Results: 477 patients were randomized (2005-2012, median FU 45.5 months). Analysis was performed after 246 progression events. Hematological toxicity ≥ grade 3 was observed in 9.4% of TMZ patients. PFS was not significantly different, median OS not reached. 1p deletion was a positive prognostic factor irrespective of treatment (p-value stratified by treatment (PFS: 0.0003;HR=0.59 95% CI(0.45-0.78)/OS: 0.002;HR=0.49 95% CI (0.32-0.77)). Conclusions: First-line treatment with TMZ compared to RT did not improve PFS in high-risk LGG patients. Although interaction test was not significant, there was a trend for inferior PFS in patients treated by TMZ with 1p intact, while OS may be better when 1p-deleted patients receive TMZ upfront. Survival analysis requires further maturation of the data. Clinical trial information: EudraCT number 2004-002714-11. [Table: see text]