Type of publication:
Sydes, M R; Spears, M R; Mason, M D; Clarke, N W; Dearnaley, D P; de Bono, J S; Attard, G; Chowdhury, S; Cross, W; Gillessen, S; Malik, Z I; Jones, R; Parker, C C; Ritchie, A W S; Russell, J M; Millman, R; Matheson, D; Amos, C; Gilson, C; Birtle, A; Brock, S; Capaldi, L; Chakraborti, P; Choudhury, A; Evans, L; Ford, D; Gale, J; Gibbs, S; Gilbert, D C; Hughes, R; McLaren, D; Lester, J F; Nikapota, A; O’Sullivan, J; Parikh, O; Peedell, C; Protheroe, A; Rudman, S M; Shaffer, R; Sheehan, D; Simms, M; *Srihari, N; Strebel, R; Sundar, S; Tolan, S; Tsang, D; Varughese, M; Wagstaff, J; Parmar, M K B; James, N D; STAMPEDE Investigators
Annals of Oncology : Official Journal of the European Society for Medical Oncology; May 2018; vol. 29 (no. 5); p. 1235-1248
Background Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: 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 versus SOC+DocP. Method Recruitment to SOC+DocP and SOC+AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for≥2years and RT to the primary tumour. Stratified randomisation allocated pts 2:1:2 to SOC; SOC+docetaxel 75mg/m2 3-weekly×6+prednisolone 10mg daily; or SOC+abiraterone acetate 1000mg+prednisolone 5mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC+AAP, and HR>1 favours SOC+DocP. Results A total of 566 consenting patients were contemporaneously randomised: 189 SOC+DocP and 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 66years and median PSA 56ng/ml. With median follow-up 4years, 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, and 40%, 7% and 1% SOC+AAP; prevalence 11% at 1 and 2 years 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 showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. 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.