key papersKey paper

NOA-08: temozolomide alone versus radiotherapy alone for malignant astrocytoma in the elderly

Older people with glioblastoma lived as long on temozolomide tablets as on radiotherapy, and the MGMT test showed who should get which: methylated tumours did better with the chemotherapy and unmethylated tumours with radiotherapy.

Randomised phase 3 non-inferiority trial of the German Neuro-oncology Working Group in 412 patients over 65 with anaplastic astrocytoma or glioblastoma, comparing dose-dense temozolomide (one week on, one week off) with radiotherapy of 60 Gy; 373 patients were treated and analysed.

Median overall survival was 8.6 months with temozolomide against 9.6 months with radiotherapy (hazard ratio 1.09), meeting non-inferiority, and event-free survival did not differ. MGMT promoter methylation was associated with longer survival and predicted benefit from temozolomide (event-free survival 8.4 against 4.6 months), while unmethylated tumours did better with radiotherapy (3.3 against 4.6 months).

Randomised controlled trialChanged practice412 participants836 citations

Authors

Wick W, Platten M, Meisner C, et al.

Published

The Lancet Oncology, 2012

Full text

doi:10.1016/S1470-2045(12)70164-X PubMed 22578793

Findings

Median overall survival 8.6 months (95% CI 7.3 to 10.2) with temozolomide versus 9.6 months (8.2 to 10.8) with radiotherapy; hazard ratio 1.09 (0.84 to 1.42), non-inferior.
MGMT promoter methylation: event-free survival 8.4 months with temozolomide versus 4.6 with radiotherapy; unmethylated: 3.3 versus 4.6 months.
More grade 3 to 4 haematological toxicity, infections and thromboembolic events with temozolomide.

What it means

With the Nordic trial, NOA-08 made MGMT testing the way to choose between temozolomide alone and radiotherapy alone for older patients with glioblastoma who are not offered combined treatment.

Caveats

Non-inferiority design with a dose-dense temozolomide schedule that is no longer standard.
The combined short-course radiotherapy plus temozolomide approach was tested separately (CE.6) and is preferred for fit older patients.