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.
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+DocP. All confidence intervals (CI) are 95%.
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.
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).
Clinical trial identification
Legal entity responsible for the study
Medical Research Council
Cancer Research UK, Medical Research Council, Janssen; Astellas, Clovis Oncology, Novartis, Pfizer, Sanofi-Aventis
M.R. Sydes: Grants and non-financial support from Janssen, Astellas, Clovis Oncology, Novartis, Pfizer, Sanofi-Aventis M.D. Mason: Personal fees and other from Sanofi, personal fees from Bayer, other from Janssen, outside the submitted work N.W. Clarke: Personal fees from Janssen Pharmaceuticals, during the conduct of the study; personal fees from Janssen Pharmaceuticals, outside the submitted work; . D. Dearnaley: Financial Support for Trial Recruitment M. Russell: Dr. Russell reports from Jannsen-Cilag, outside the submitted work. R. Jones: Personal fees and non-financial support from Janssen, grants, personal fees and other from Astellas, outside the submitted work. J. de Bono: Employee of the ICR which has a commercial interest in abiraterone. Has served on Janssen Advisory Board as a consultant. 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. S. Chowdhury: Personal fees from Janssen Paharmaceutical, outside the submitted work; . J. Lester: Personal fees, non-financial support and other from Janssen, personal fees, non-financial support and other from Astellas, outside the submitted work. M.K. Parmar: Jansenn: Unrestricted grant to contribute to this comparison of STAMPEDE which supports the protocol overall, plus abiraterone and distribution. N.D. 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 All other authors have declared no conflicts of interest.