Wick W et al. – Temozolomide alone is non–inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision–making.

• Between May 15, 2005, and Nov 2, 2009, the authors enrolled patients with confirmed anaplastic astrocytoma or glioblastoma, age older than 65years, and a Karnofsky performance score of 60 or higher.
• Patients were randomly assigned 100mg/m² temozolomide, given on days 1-7 of 1week on, 1week off cycles, or radiotherapy of 60.0Gy, administered over 6-7weeks in 30 fractions of 1.8-2.0Gy.
• The primary endpoint was overall survival.
• They assessed non-inferiority with a 25% margin, analysed for all patients who received at least one dose of assigned treatment.

• Of 584 patients screened, the authors enrolled 412.
• 373 patients (195 randomly allocated to the temozolomide group and 178 to the radiotherapy group) received at least one dose of treatment and were included in efficacy analyses.
• Median overall survival was 8.6months (95% CI 7.3-10.2) in the temozolomide group versus 9.6months (8.2-10.8) in the radiotherapy group (hazard ratio [HR] 1.09, 95% CI 0.84-1.42, pnon-inferiority=0.033).
• Median event-free survival (EFS) did not differ significantly between the temozolomide and radiotherapy groups (3.3months [95% CI 3.2-4.1] vs 4.7 [4.2-5.2]; HR 1.15, 95% CI 0.92-1.43, pnon-inferiority=0.043).
• Tumour MGMT promoter methylation was seen in 73 (35%) of 209 patients tested.
• MGMT promoter methylation was associated with longer overall survival than was unmethylated status (11.9months [95% CI 9.0 to not reached] vs 8.2months [7.0-10.0]; HR 0.62, 95% CI 0.42-0.91, p=0.014).
• EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy (8.4months [95e% CI 5.5—11.7] vs 4.6 [4.2—5.0]), whereas the opposite was true for patients with no methylation of the MGMT promoter (3.3 months [3.0-3.5] vs 4.6months [3.7-6.3]).
• The most frequent grade 3-4 intervention-related adverse events were neutropenia (16 patients in the temozolomide group vs two in the radiotherapy group), lymphocytopenia (46 vs one), thrombocytopenia (14 vs four), raised liver-enzyme concentrations (30 vs 16), infections (35 vs 23), and thromboembolic events (24 vs eight).