26 Background: Long-term hormone therapy (HT) alone is standard of care for men with metastatic or high-risk non-metastatic prostate cancer (PCa). STAMPEDE investigates whether early use of additional therapies improves overall survival. It is an international randomised controlled trial ( NCT00268476 ) using novel multi-arm, multi-stage methods to assess adding 1 or 2 of three agents (docetaxel, zoledronic acid (ZA), celecoxib) in 5 research arms in men with PCa starting long-term HT for the first time. Methods: HT was given as per standard care. Celecoxib was planned as 400mg bid until the sooner of 1 year or disease (including PSA) progression. The trial has 3 intermediate activity stages (I-III) where the outcome measure (OM) is failure-free survival (FFS) and 1 final efficacy stage (IV) with overall survival as primary OM. At the end of each stage, research arms are compared pairwise to the control arm. Accrual of further patients is discontinued early for any research arm either showing (a) safety concerns or (b) insufficient evidence of activity (lack-of-benefit) where the treatment effect on FFS is compared against a pre-defined stopping guideline. The interim activity “hurdle” becomes increasingly stringent stage-by-stage. Results: From Oct-2008 to Feb-2011, 2114 patients were consented and randomised, including 875 in this comparison. With 205 control FFS events, there was evidence of insufficient activity for HT+celecoxib over HT-alone: HR 0.98 (95%CI 0.90-1.06). The Independent Data Monitoring Committee recommended stopping accrual to this arm; stopping celecoxib was also recommended for patients currently on treatment. (Accrual was also stopped to HT+celecoxib+ZA but data are not disclosed.) There was no evidence of differences in toxicity: 25% and 23% of patients reporting grade ≥3 toxicities or adverse events with or without celecoxib. Control arm FFS was 51% at 2 years, in line with expectations. Conclusions: Celecoxib shows no evidence of activity in this setting. Accrual continues seamlessly to the other research arms. Follow-up of all arms is ongoing. Support: MRC, Cancer Research UK, Novartis, Sanofi-Aventis, Pfizer.
Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial
