Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: First overall survival results from STAMPEDE(NCT00268476)
1University of Warwick, Coventry, UK,2MRC Clinical Trials Unit at UCL, London, UK,3Velindre Hospital, Cardiff, UK,4The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK,5Beatson West of Scotland Cancer Centre, Glasgow, UK,6Clatterbridge Cancer Centre, Wirral, UK,7South West Wales Cancer Institute, Swansea, UK,8University of Oxford Medical Oncology Department, Oxford, UK,9Royal Devon and Exeter NHS Foundation Trust, Exeter, UK,10Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK,11Belfast City Hospital, Belfast, UK,12Kantonsspital Chur, Chur, Switzerland,13Queen Elizabeth Hospital, Birmingham, UK,14The Christie and Salford Royal Hospitals, Manchester, UK,15Prostate Cancer Support Group, Middlesbrough, UK
STAMPEDE is a randomised controlled trial using a novel multi-arm multi-stage design. It recruits men (pts) with high-risk locally advanced or metastatic prostate cancer (PCa) starting long-term hormone therapy (HT) for the first time. The trial initially assessed adding 1 or 2 of 3 treatment approaches to standard of care (SOC). We report primary survival results for 3 research comparisons that recruited through all their intermediate analyses: docetaxel (D), zoledronic acid (ZA) & the combination (D+ZA).
SOC was hormone therapy for >= 3yrs; RT was encouraged for N0M0 pts up to Nov-2011, then mandated; RT was optional for N+M0 pts. Stratified randomisation allocated pts 2:1:1:1 to SOC (control), SOC+D, SOC+ZA or SOC+D+ZA. 4mg ZA was given for six 3-weekly cycles then 4-weekly until 2yrs. D was given as 75mg/m2 for six 3-weekly cycles with prednisolone 10mg daily. The primary outcome measure was survival (time from randomisation to death from any cause). Pairwise comparisons to control on survival for each research arm had 90% power at 2.5% 1-sided alpha for a hazard ratio of 0.75 requiring ~400 control arm deaths, accounting for 3 intermediate lack?of?benefit analyses on failure-free survival. Analyses used the Cox model of the logrank test, adjusted for stratification factors.
From Oct-2005 to Mar-2013, 2,962 pts were randomised to the 4 arms. The groups were balanced with median age 65yrs; 61% metastatic, 14% N+/XM0, 22% N0M0; 93% diagnosed within 6m of randomisation; median PSA 65ng/ml. Median follow-up was 42m. Grade 3-5 toxicity was reported for 31% SOC, 50% SOC+D, 32% SOC+ZA and 52% SOC+D+ZA.There were 405 deaths on the control arm (84% from PCa). The hazard ratio was 0.76 (95% CI 0.63, 0.91; p = 0.003) for SOC+D vs SOC; 0.93 (95% CI 0.79, 1.11; p = 0.437) for SOC+ZA vs SOC; and 0.81 (95% CI 0.68, 0.97; p = 0.020) for SOC+D+ZA vs SOC. Median survival was increased by 1yr from 67m on SOC to 77m on SOC+D. Results in M0 and M1 disease will be shown.
Survival data from STAMPEDE show a clinically and statistically significant improvement in survival from adding docetaxel but not from adding zoledronic acid in men starting long-term hormone therapy for the first time.