A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677)

• Published in: Journal of clinical oncology Vol. 30; no. 15_suppl; p. TPS2104
• Main Authors: Perry, James R., O'Callaghan, Christopher J, Ding, Keyue, Roa, Wilson, Mason, Warren P., Cairncross, J. Gregory, Brandes, Alba Ariela, Menten, Johan, Phillips, Claire, Fay, Michael F., Nishikawa, Ryo, Winch, Chad, Laperriere, Normand
• Format: Journal Article
• Language: English
• Published: 20-05-2012
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2012.30.15_suppl.tps2104

Abstract only
TPS2104
Background: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly diagnosed GBM found improved survival with concomitant and adjuvant temozolomide (TMZ) added to radiotherapy (RT). Study pts were 18-71 (median 56) years; however a sub-group analysis noted a trend of decreasing benefit from the addition of TMZ with increasing age, such that for age 65-71, the hazard ratio of 0.8 did not reach statistical significance (p=0.340). Recent RCTs in elderly GBM found improved survival with RT compared to supportive care alone and detected non-inferiority of 40 Gy/15 vs. a 60 Gy/30 RT regimen. Based upon these results short-course hypofractionated RT is often recommended for elderly pts. However, whether the addition of TMZ to RT confers a survival advantage in elderly pts remains unanswered. Methods: Patients ≥65 yrs of age with histologically confirmed newly diagnosed glioblastoma, ECOG 0-2, are randomized 1:1 to receive 40Gy/15 RT vs. 40Gy/15 RT with 3 weeks of concomitant temozolomide plus monthly adjuvant TMZ until progression or 12 cycles. Stratification is by centre, age (65-70, 71-75, or 76+), ECOG 0,1 vs 2, and biopsy vs resection. For 90% power to detect a 25% reduction in the primary outcome of overall survival (increased MST from 6 to 8 months) between arms, using a two-sided 5% alpha, a minimum of 520 deaths must be observed prior to analysis; total sample size is 560 patients. The trial is open in Canada (NCIC CTG), Europe (EORTC), Australia and New Zealand (TROG), and Japan. As of Jan 25, 2012, 361 (65%) of the target 560 pts were randomized (147 Canada, 144 Europe, 64 Australasia, 6 Japan). Median age of randomized patients is 73 (65-88) years. A planned futility analysis after 120 events by the independent DSMB resulted in a recommendation that the trial continue.Accrual is expected to be complete in 2013. A comprehensive molecular companion analysis, including MGMT promoter methylation, is planned.