Celecoxib with or without zoledronic acid for hormone-naïve prostate cancer: Survival results from STAMPEDE (NCT00268476).

162 Background: STAMPEDE is a randomised controlled trial using a 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 one or two of three treatment approaches to standard-of-care (SOC). We report comparative survival data for the two original comparisons that stopped accrual early at pre-planned lack-of-activity analysis based on failure-free survival (FFS): celecoxib (Cox) and celecoxib + zoledronic acid (Cox+ZA). Methods: SOC was HT for at least 2yrs; RT was encouraged for men with M0 disease. Stratified randomisation allocated pts 2:1:1 to SOC (control), SOC+Cox or SOC+Cox+ZA. Celecoxib (400mg) was given twice daily until 1yr. Zoledronic acid (4mg) was given for six 3-weekly cycles then 4-weekly until 2yrs. The primary outcome measure was death from any cause. This pre-planned analysis is triggered by analysis of the “original comparisons” that continued accrual through all activity stages. Analyses use Cox proportional hazards model and flexible parametric models, all adjusted for stratification factors. Results: 1,245 men were contemporaneously randomised to these 3 arms (Oct2005-Apr2011). Groups were well balanced: median age 65yrs; 61% metastatic, 14% N+/X M0, 25% N0M0; 94% newly-diagnosed; median PSA 66ng/ml. Median follow-up was 62m. Grade 3-5 adverse events were seen in 35% SOC, 32% SOC+Cox, 32% SOC+Cox+ZA. There were 295 control arm deaths (82% PCa); median survival 68m. The adjusted HR was 1.00 (95% CI 0.82-1.22; p=0.99; median OS 69m) for SOC+Cox vs SOC; and 0.86 (95%CI 0.70-1.06; p=0.16; median OS 74m) for SOC+Cox+ZA vs SOC. Pre-planned analyses in men with metastatic disease showed HR 0.78 (95%CI 0.62-0.99) for SOC+Cox+ZA vs SOC. Further data will be shown. Conclusions: These data show no survival advantage for the addition of celecoxib alone for men starting long-term HT for the 1 st time. However, the addition of celecoxib combined with ZA demonstrated a survival advantage for men with metastatic disease, in a pre-planned analysis, and requires further investigation. Clinical trial information: NCT00268476.