Radiotherapy with or without concomitant and adjuvant temozolomide in newly diagnosed glioblastoma (EORTC 26981-22981 / NCIC CE.3): trial

Radiotherapy with or without concomitant and adjuvant temozolomide in newly diagnosed glioblastoma (EORTC 26981-22981 / NCIC CE.3)

Population

Adults with newly diagnosed, histologically confirmed glioblastoma; median age 56 years and 84 percent had undergone debulking surgery (primary report)

Design

Randomised phase 3 trial: radiotherapy alone (fractionated focal irradiation, 2 Gy daily, 5 days a week for 6 weeks, 60 Gy in total) versus the same radiotherapy plus continuous daily temozolomide 75 mg/m2 followed by six adjuvant cycles (150 to 200 mg/m2 for 5 days of each 28-day cycle); primary endpoint overall survival; randomisation between 17 Aug 2000 and 22 Mar 2002 per the 5-year analysis abstract

Primary endpoint

Arms

Radiotherapy alone (control, n = 286): Radiotherapy 60 Gy in 2 Gy fractions
Radiotherapy plus temozolomide (experimental, n = 287): Radiotherapy 60 Gy in 2 Gy fractions with daily temozolomide 75 mg/m2, then six adjuvant cycles of temozolomide

People

Stupp R, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups and National Cancer Institute of Canada Clinical Trials Group

OSHR 0.63 (95% CI 0.52–0.75)Δ median OS+2.5 monthsΔ 24-month OS+16.1 pointsOSHR 0.6 (95% CI 0.5–0.7)Δ 24-month OS+16.3 points

Show the numbers

Results reported for Radiotherapy with or without concomitant and adjuvant temozolomide in newly diagnosed glioblastoma (EORTC 26981-22981 / NCIC CE.3)
Endpoint	Analysis	Radiotherapy plus temozolomide	Radiotherapy alone	Effect
OSAll randomised patients (n=573); analysis population not otherwise specified in the abstract	primarymedian follow-up 28 monthsStupp 2005	median 14.6 months; 26.5% at 2 y	median 12.1 months; 10.4% at 2 y	HR 0.63 (95% CI 0.52–0.75)P<0.001The abstract calls the hazard ratio unadjusted (hazard ratio for death with radiotherapy plus temozolomide). The paper randomised 573 patients; the ClinicalTrials.gov record NCT00006353 lists 575 enrolled.
OS	long term-updateStupp 2009	27.2% at 2 y (22.2–32.5%); 16% at 3 y (12.0–20.6%); 12.1% at 4 y (8.5–16.4%); 9.8% at 5 y (6.4–14.0%)	10.9% at 2 y (7.6–14.8%); 4.4% at 3 y (2.4–7.2%); 3% at 4 y (1.4–5.7%); 1.9% at 5 y (0.6–4.4%)	HR 0.6 (95% CI 0.5–0.7)P<0.0001Five-year analysis with a median follow-up of more than 5 years per the abstract. The 2-year estimate here (27.2% vs 10.9%) differs from the primary report (26.5% vs 10.4%) because it comes from the longer-follow-up analysis; the abstract does not explain the difference. Hazard ratio given to one decimal place in the abstract.

Results reported for Radiotherapy with or without concomitant and adjuvant temozolomide in newly diagnosed glioblastoma (EORTC 26981-22981 / NCIC CE.3)
Endpoint	Analysis	Radiotherapy plus temozolomide	Radiotherapy alone	Effect
OSAll randomised patients (n=573); analysis population not otherwise specified in the abstract	primarymedian follow-up 28 monthsStupp 2005	median 14.6 months; 26.5% at 2 y	median 12.1 months; 10.4% at 2 y	HR 0.63 (95% CI 0.52–0.75)P<0.001The abstract calls the hazard ratio unadjusted (hazard ratio for death with radiotherapy plus temozolomide). The paper randomised 573 patients; the ClinicalTrials.gov record NCT00006353 lists 575 enrolled.
OS	long term-updateStupp 2009	27.2% at 2 y (22.2–32.5%); 16% at 3 y (12.0–20.6%); 12.1% at 4 y (8.5–16.4%); 9.8% at 5 y (6.4–14.0%)	10.9% at 2 y (7.6–14.8%); 4.4% at 3 y (2.4–7.2%); 3% at 4 y (1.4–5.7%); 1.9% at 5 y (0.6–4.4%)	HR 0.6 (95% CI 0.5–0.7)P<0.0001Five-year analysis with a median follow-up of more than 5 years per the abstract. The 2-year estimate here (27.2% vs 10.9%) differs from the primary report (26.5% vs 10.4%) because it comes from the longer-follow-up analysis; the abstract does not explain the difference. Hazard ratio given to one decimal place in the abstract.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.63	0.52–0.75
OS	0.6	0.5–0.7

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Radiotherapy alone (control)
Radiotherapy plus temozolomide (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Radiotherapy alone	Radiotherapy plus temozolomide
0	100.0%	100.0%
9	59.7%	65.2%
18	35.7%	42.5%
27	21.3%	27.8%
37	12.0%	17.3%

Illustrative — modelled from reported values, not trial data. OS, long term-update.

Show curves

Radiotherapy alone (control)
Radiotherapy plus temozolomide (experimental)

Data table (modelled values)

Months	Radiotherapy alone	Radiotherapy plus temozolomide
0	100.0%	100.0%
16	33.1%	47.7%
32	5.1%	18.3%
49	2.9%	11.9%
65	1.9%	9.8%

Appears in

2005 Temozolomide added to radiotherapy for newly diagnosed glioblastoma

Sources

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-96.
PubMed DOI
Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459-66.
PubMed DOI