Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.
Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP vs SOC+DocP. Method: Recruitment to SOC+DocP and SOC+AAP overlapped Nov-2011─Mar-2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2yrs and RT to the primary tumour. Stratified randomisation allocated pts 2:1:2 to SOC; SOC+docetaxel 75mg/m2 3-weekly x6 + prednisolone 10mg daily; or SOC+abiraterone acetate 1000mg + prednisolone 5mg daily. AAP duration depended on stage & intent to give radical RT. The 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. A hazard ratio (HR)<1 favours SOC+AAP, HR > 1 favours SOC+DocP. Results: 566 consenting patients were contemporaneously randomised: 189 SOC+DocP, 377 SOC+AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66yr & median PSA 56ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1·16 (95%CI 0·82-1·65); failure-free survival HR = 0·51 (95%CI 0·39-0·67); progression-free survival HR = 0·65 (95%CI 0·48-0·88); metastasis-free survival HR = 0·77 (95%CI 0·57-1·03); prostate cancer-specific survival HR = 1·02 (0·70-1·49); and symptomatic skeletal events HR = 0·83 (95%CI 0·55-1·25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC+DocP, & 40%, 7% and 1% SOC+AAP; prevalence 11% at 1 and 2yrs on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer (HNPC) showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events, suggesting that Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.