Background
Five-year follow-up report of the EORTC-NCIC phase III trial (EORTC 26981/22981) that established the Stupp regimen. 573 patients originally enrolled; 5-year analysis with median follow-up >5 years. Primary purpose: to determine whether early survival gains from TMZ+RT persisted at 5 years.
Interventions and follow up
Arm A: Radiotherapy alone — 60 Gy in 30 fractio
Arm B: Radiotherapy + concurrent + adjuvant temozolomide (Stupp regimen)
Primary endpoint: Overall survival (long-term follow-up)
mFollow up: Median >5 years (278/286 RT-alone and 254/287 TMZ+RT patients died)
Arm B: Radiotherapy + concurrent + adjuvant temozolomide (Stupp regimen)
Primary endpoint: Overall survival (long-term follow-up)
mFollow up: Median >5 years (278/286 RT-alone and 254/287 TMZ+RT patients died)
Results
5-year OS rate: 9.8% (TMZ+RT) vs 1.9% (RT alone)
4-year OS: 12.1% vs 3.0%
3-year OS: 16.0% vs 4.4%
OS HR: 0.6 (95% CI 0.5–0.7), P<.0001
MGMT methylated (5-yr OS): ~16% vs ~4%
4-year OS: 12.1% vs 3.0%
3-year OS: 16.0% vs 4.4%
OS HR: 0.6 (95% CI 0.5–0.7), P<.0001
MGMT methylated (5-yr OS): ~16% vs ~4%
Adverse events
Main adverse events: Long-term toxicity analysis showed no late treatment-related serious AEs attributable to TMZ not previously identified. Rare long-term survivors (5+ years) most commonly had MGMT-methylated tumors.
Conclusions
The survival benefit of TMZ+RT was durable at 5 years, with 9.8% vs 1.9% alive at 5 years — confirming that a meaningful subset of patients achieve long-term survival. MGMT methylation was the strongest prognostic factor; these patients derived most benefit from TMZ.
Key Limitations
Key Limitations: MGMT analysis limited to 206/573 assessable patients — not all tumors had tissue available. Benefit in MGMT-unmethylated tumors remains uncertain. No crossover arm. Open-label design. The small absolute numbers of 5-year survivors (approximately 28 in TMZ+RT arm) limit conclusions about predictors of exceptional response.
Clinical Context
This 5-year update reinforced TMZ+RT as standard of care and established that GBM, while almost universally fatal, can have rare long-term survivors — typically MGMT-methylated and young. MGMT methylation testing became standard practice globally after this report. Regulatory label for temozolomide in GBM is based on the original 2005 NEJM paper plus this 5-year confirmation.
References