Adding abiraterone for patients (pts) with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): Outcomes in non-metastatic (M0) patients from STAMPEDE (NCT00268476)

Abstract

Background: Abiraterone acetate and prednisolone (AAP) improved survival in men with castration-refractory PCa; we assessed it earlier in the disease. STAMPEDE is a randomised controlled trial using a multi-arm multi-stage platform design, recruiting pts starting long-term ADT with high-risk locally advanced or metastatic PCa. The overall survival advantage of HR=0.63 was dominated by deaths in M1 pts. We focus on outcomes in the "AAP comparison" pt subgroup with M0 disease at randomisation. Method(s): Standard-of-care (SOC) was ADT for 2+yr; radiotherapy (RT) was mandated for N0M0 disease (unless contraindicated) & encouraged for N+M0. Stratified randomisation allocated pts 1:1 to SOC or SOC+abiraterone acetate 1000mg +prednisolone 5mg daily (SOC+AAP). AAP continued to PSA, radiological & clinical progression, capped at 2 years in pts having radical RT. The definitive primary outcome measure (OM) was death from any cause; Failure-Free Survival (FFS) was the intermediate primary OM. Secondary OMs included Metastasis-Free Survival (MFS). Analyses used Cox proportional hazards, adjusted for stratification factors. Result(s): 915M0 pts were randomised to SOC or SOC+AAP fromNov 2011 to Jan 2014: median age 67 yr (IQR 44-84); 81%WHOPS 1; 42%N+M0; 82% planned to receive SOC RT; median follow-up 38m.N0M0 pts not planned for RT (previously treated or contraindication) are not excluded fromsubgroup estimates. FFS was improved in SOC+AAP inN0M0: HR=0.14 (95%CI 0.07-0.30)with 3yr FFS 80%SOC vs 98% SOC+AAP. InN+M0, FFS was improved on SOC+AAPHR=0.26 (95%CI 0.17-0.40), translating into an effect on survival consistent with the overall trial estimate, HR=0.67 (95%CI 0.39- 1.17). Estimates ofMFS are favourable for SOC+AAP within both subgroups; N0M0HR=0.62 (95%CI CI 0.33-1.14), N+M0HR=0.47 (95%CI 0.29-0.78). Survival estimates inN0M0 pts are immature, with only 26 deaths. Conclusion(s): Early clinical outcomes for all M0 pts who had AAP are excellent, particularly in N0M0 pts also planned for RT. The models from the ICECaP project suggest that MFS improvements of this magnitude in M0 pts should translate into a survival advantage.