Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year …

R Stupp, ME Hegi, WP Mason, MJ Van Den Bent… - The lancet …, 2009 - thelancet.com
R Stupp, ME Hegi, WP Mason, MJ Van Den Bent, MJB Taphoorn, RC Janzer, SK Ludwin…
The lancet oncology, 2009thelancet.com
Background In 2004, a randomised phase III trial by the European Organisation for
Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada
Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with
glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We
report the final results with a median follow-up of more than 5 years. Methods Adult patients
with newly diagnosed glioblastoma were randomly assigned to receive either standard …
Background
In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years.
Methods
Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353.
Findings
Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27ˇ2% (95% CI 22ˇ2–32ˇ5) at 2 years, 16ˇ0% (12ˇ0–20ˇ6) at 3 years, 12ˇ1% (8ˇ5–16ˇ4) at 4 years, and 9ˇ8% (6ˇ4–14ˇ0) at 5 years with temozolomide, versus 10ˇ9% (7ˇ6–14ˇ8), 4ˇ4% (2ˇ4–7ˇ2), 3ˇ0% (1ˇ4–5ˇ7), and 1ˇ9% (0ˇ6–4ˇ4) with radiotherapy alone (hazard ratio 0ˇ6, 95% CI 0ˇ5–0ˇ7; p<0ˇ0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60–70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy.
Interpretation
Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide.
Funding
EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.
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