For this trial, standard of care was ADT for 2+ years, and radiotherapy was mandated for patients with N0M0 disease (unless contraindicated) and encouraged for patients with N+M0. Stratified randomization allocated patients 1:1 to ADT or ADT + abiraterone acetate 1000mg + prednisolone 5mg daily. Abiraterone treatment continued to PSA, radiological and clinical progression, capped at 2 years in patients receiving radiotherapy. The definitive primary outcome measure was death from any cause and failure-free survival (FFS) was the intermediate primary outcome measure. Secondary outcomes included metastasis-free survival (MFS). Analyses used Cox proportional hazards, adjusted for stratification factors.
There were 915 M0 patients who were randomized to ADT or ADT + abiraterone + prednisolone from November 2011 to January 2014. The median age was 67 years (IQR 44-84), 81% were WHO performance status 1, 42% had N+M0 disease, and median follow-up was 38 months. N0M0 patients not planned for radiotherapy (previously treated or contraindication) were not excluded from subgroup estimates. FFS was improved in ADT + abiraterone in N0M0 patients compared to ADT alone (HR 0.14, 95%CI 0.07-0.30), with 3-year FFS of 80% for ADT alone vs 98% for ADT + abiraterone. In N+M0 patients, FFS was also improved on ADT + abiraterone compared to ADT alone (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 favorable for ADT + abiraterone 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.
The authors concluded that early clinical outcomes for all M0 patients who had ADT + abiraterone are excellent, particularly in N0M0 patients also planned for radiotherapy. As suggested from recently reported findings from the ICECaP working group , MFS improvements of this magnitude in M0 patients should translate into a survival advantage.
Speaker: Nicholas D. James, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom
Co-Authors: J. De Bono (Sutton, United Kingdom) M. R. Spears (WCB NH, United Kingdom) N. W. Clarke (M HD, United Kingdom) M. D. Mason (Cardiff, United Kingdom) D. Dearnaley (Sutton, United Kingdom) A. W. Ritchie (London, United Kingdom) M. Russell (Glasgow, United Kingdom) C. Gilson (London, United Kingdom) R. Jones (Glasgow, United Kingdom)
S. Gillessen (Switzerland, Switzerland) D. Matheson (WCB NH, United Kingdom) S. Aung (Devon, United Kingdom) A. Birtle (Preston, United Kingdom) S. Chowdhury (London, United Kingdom) J. Gale (Portsmouth, United Kingdom) Z. Malik (Clatterbridge, United Kingdom) J. O'Sullivan (Belfast, United Kingdom) M. K. Parmar (London, United Kingdom) M. R. Sydes (London, United Kingdom)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain
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