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).

Abstract

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.