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.
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.
915 M0 pts were randomised to SOC or SOC+AAP from Nov 2011 to Jan 2014: median age 67 yr (IQR 44-84); 81% WHO PS 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 from subgroup estimates. FFS was improved in SOC+AAP in N0M0: HR = 0.14 (95%CI 0.07-0.30) with 3yr FFS 80% SOC vs 98% SOC+AAP. In N+M0, FFS was improved on SOC+AAP HR = 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 of MFS are favourable for SOC+AAP within both subgroups; N0M0 HR=0.62 (95%CI CI 0.33-1.14), N+M0 HR=0.47 (95%CI 0.29-0.78). Survival estimates in N0M0 pts are immature, with only 26 deaths.
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.
Clinical trial identification
Legal entity responsible for the study
UK Medical Research Council
MRC, CRUK, Janssen; Astellas, Clovis Oncology, Novartis, Pfizer, Sanofi Aventis
N. James: Grants, personal fees and non-financial support from Janssen, Astellas, Sanofi, Novartis during the conduct of the study; grants and non-financial support from Clovis Oncology, Pfizer. J. de Bono: Other from AstraZeneca, Glaxosmithkline, Pfizer, Taiho, Daiichi, Novartis, Genmab, Merck Serano, Merck, Genentech/Roche. Has a patent null pending. N.W. Clarke: Personal fees from Janssen Pharmaceuticals, during the conduct of the study. Personal fees from Janssen Pharmaceuticals, outside the submitted work. M.D. Mason: Personal fees and other from Sanofi, personal fees from Bayer, other from Janssen, outside the submitted work. D. Dearnaley: UK National Institute for Health Research Clinical Research Network, Janssen Pharma, Sandoz Pharmaceuticals, Cadence Research, Janssen-Cilag, ISSECAM, other from Clovis. Royalties from a patent GB9305269 – 17. M. Russell: Janssen-Cilag, outside the submitted work. C. Gilson: Grants from Clovis Oncology, outside the submitted work. R. Jones: Personal fees and non-financial support from Janssen and Astellas, outside the submitted work. S. Gillessen: Bayer, CureVac, Janssen Cilag, Dendreon Corp, Astellas, Millennium Pharmaceuticals, Orion, Sanofi, MaxiVax SA, AAA, Bristol-Myers Squibb, Ferring, Roche, Innocrin Pharmaceuticals, Nektar Therapeutics, ProteoMedix. A. Birtle: Advisory boards to disclose with Astellas, Janssen, Sanofi and outside of relevant work with AstraZeneca and Bayer. S. Chowdhury: Personal fees from Janssen Paharmaceutical, outside the submitted work. Z. Malik: Consultancy and advisory boards Janssen, Sanofi and Astellas Sponsorship to attend medical conferences Astellas, Bayer and Janssen. J. O\'Sullivan: Personal fees from Janssen, outside the submitted work. M.K. Parmar: Grants and non-financial support from Janssen, Astellas, Clovis Oncology, Novartis, Pfizer, Sanofi-Aventis, outside the submitted work. M.R. Sydes: Grants and non-financial support from Janssen, Astellas, Clovis Oncology, Novartis, Pfizer, Sanofi-Aventis. All other authors have declared no conflicts of interest.