ESMO 2017: Adding abiraterone acetate plus prednisolone or docetaxel for patients with high-risk prostate cancer starting long-term androgen deprivation therapy: directly randomized data from STAMPEDE

Madrid, Spain (UroToday.com)  Dr. Matthew Sydes and colleagues presented directly randomized data from STAMPEDE assessing abiraterone + prednisolone vs docetaxel + prednisolone for patients with high-risk prostate cancer starting androgen deprivation therapy (ADT). Previously, data from STAMPEDE has shown that adding abiraterone + prednisolone [1] or adding docetaxel + prednisolone [2] to standard of care ADT both improved survival vs standard of care ADT. STAMPEDE is a multi-arm, multi-stage platform randomized controlled protocol recruiting patients with high risk, locally advanced or metastatic prostate cancer starting long-term ADT. The objective of this study was to assess direct, randomized data of ADT + abiraterone + prednisolone or ADT + docetaxel + prednisolone using a STAMPEDE subset.

In this study, recruitment to the “docetaxel comparison” and “abiraterone comparison” overlapped from November 2011 to January 2014. Standard of care was long term ADT or 2+ years of ADT with radiotherapy (for some M0). Stratified randomization allocated patients 2:1:2 to standard of care (ADT), or ADT + docetaxel 75mg/m2 3-weekly x6 + prednisolone 5mg twice daily, or ADT + abiraterone acetate 1000mg + prednisolone 5mg daily. Abiraterone + prednisolone duration depended on stage and intent for radical radiotherapy. The primary outcome was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This study was not a formally powered comparison. Although power was limited, the authors stated that it is indicative of a likely magnitude of difference if HR < 1 favors ADT + abiraterone, or HR > 1 favors ADT + docetaxel. There were 566 patients randomized to ADT + docetaxel (n=189; the last of 592 ADT + docetaxel patients) and ADT + abiraterone (n=377; the first of 960 ADT + abiraterone patients). Groups were well balanced with 342 (60%) patients with M1 disease, 429 (76%) patients with Gleason 8-10 disease, 449 (79%) patients with WHO performance status 0, a median age 66 years and a median PSA 56 ng/ml. At a median follow up 4 years, there were 149 deaths: 45 (23.8%) receiving ADT + docetaxel and 111 (29.4%) receiving ADT + abiraterone. The survival HR was 1.16 (95%CI 0.82-1.65), failure free survival HR was 0.51 (95%CI 0.39-0.67), progression free survival HR was 0.65 (95%CI 0.48-0.88), metastases free survival HR was 0.77 (95%CI 0.57-1.03), and skeletal related event survival HR was 0.83 (95%CI 0.55-1.25). There was no heterogeneity by baseline M0/M1. Grade 3, 4, 5, toxicity was 36%, 13%, 1% for ADT + docetaxel, respectively, and 40%, 7%, 1% for ADT + abiraterone, respectively. Subsequent treatments varied by arm, with much crossing over after progression.

The authors concluded that in this direct, randomized, comparative analysis of two new standards for care for high-risk, hormone naïve prostate cancer, failure free survival and progression free survival clearly favored ADT + abiraterone. Although not statistically significant, ADT + abiraterone also favored metastasis free survival and skeletal related event survival, while overall survival favored ADT + docetaxel. Ultimately, at this point, drug availability may be the most common driver of treatment choice.

Speaker: Matthew R. Sydes, University College London, London, United Kingdom

Co-Authors: M. D. Mason (Cardiff, United Kingdom) M. R. Spears (London, United Kingdom) N. W. Clarke (M HD, 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) J. De Bono (Sutton, United Kingdom) S. Gillessen (Switzerland, Switzerland) R. Millman (WCB NH, United Kingdom) S. Tolan (Wirral, United Kingdom) J. Wagstaff (Swansea, United Kingdom) S. Chowdhury (London, United Kingdom) J. Lester (Wales, United Kingdom) D. Sheehan (Exeter, United Kingdom) J. Gale (Portsmouth, United Kingdom) M. K. Parmar (London, United Kingdom) N. D. James (Birmingham, 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

References:

1. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377(4):338-351.
2. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163-1177.
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