Adding abiraterone acetate plus prednisolone (AAP) or docetaxel for patients (pts) with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): Directly randomised data from STAMPEDE (NCT00268476)

Abstract

Background: Adding abiraterone acetate + prednisone (AAP) & adding docetaxel + prednisone (DocP) to standard of care (SOC) each improved survival vs SOC in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting pts with high risk locally advanced or metastatic PCa starting long-term ADT. We share the first direct, randomised data of SOC+AAP or SOC+DocP using a STAMPEDE subset. Methods: Recruitment to the “DocP comparison” & “AAP comparison” overlapped Nov2011 - Jan2014. SOC was long term ADT or 2+yr ADT with RT (for some M0). Stratified randomisation allocated pts 2:1:2 to SOC : or SOC + Doc 75mg/m2 3-weekly x6 + P 5mg twice daily : or SOC + AA 1000mg + P 5mg daily. AAP duration depended on stage & intent for radical RT. Primary outcome measure was death from any cause. Analyses used Cox proportional hazards & flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison; power is limited, but is indicative of the likely magnitude of difference: HR<1 favours SOC+AAP, HR>1 favours SOC+DocP. All confidence intervals (CI) are 95%. Results: 566 pts were contemporaneously randomised: 189 SOC+DocP (the last of 592 SOC+DocP pts) & 377 SOC+AAP (the first of 960 SOC+AAP pts). Groups were well balanced with 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO PS 0; median age 66yr & PSA 56ng/ml. At median follow up 4 yr, there were 149 deaths (45 SOC+Doc, 111 SOC+AAP): survival HR 1.16 (0.82-1.65); failure free survival HR= 0.51 (0.39-0.67); progression free survival HR 0.65 (0.48-0.88); metastases free survival HR 0.77 (0.57-1.03); & SRE HR 0.83 (0.55-1.25). There was no heterogeneity by baseline M0/M1. Grade 3, 4, 5 toxicity was 36%, 13%, 1% SOC+DocP, & 40%, 7%, 1% SOC+AAP. Subsequent treatments varied by arm, with much crossing after progression. Conclusions: In this direct, randomised, comparative analysis of 2 new standards for HNPC, FFS & PFS clearly favoured SOC+AAP &, with less certainty, MFS & SRE favoured SOC+AAP & survival SOC+Doc. Worst toxicity grade was similar. Drug availability may drive treatment choice. Published STAMPEDE data also contribute to a network MA (#2871).