ESMO 2017: Indirect Comparison of Abiraterone Acetate and Docetaxel for Treatment of Metastatic “Hormone-Sensitive” Prostate Cancer

Madrid, Spain (UroToday.com) Androgen deprivation therapy (ADT) with or without chemotherapy (docetaxel) [1-3] is recommended in the clinical guidelines as the mainstay of management for metastatic hormone-sensitive prostate cancer (mHSPC). However, the LATITUDE [4] and STAMPEDE [5] trials recently demonstrated the efficacy of abiraterone acetate in combination with prednisone and ADT vs ADT alone in newly diagnosed mHSPC patients with high-risk disease. Dr. Feyerabend and colleagues presented their indirect comparison of abiraterone and docetaxel treatment of metastatic hormone sensitive prostate cancer at this afternoon’s poster session at ESMO 2017 in Madrid, Spain. The objective of this study was to indirectly compare abiraterone and docetaxel in the mHSPC setting to further determine relative efficacy.
 
The authors conducted a systematic literature review of randomized controlled trials (RCTs) assessing treatments for mHSPC. To increase comparability of results across studies, the population of interest from LATITUDE [4] and docetaxel studies was restricted to men with newly diagnosed high-risk disease and/or high-volume disease. Two RCTs (CHAARTED [2], GETUG-AFU 15 [1]), both evaluating ADT alone vs docetaxel + ADT, met the inclusion criteria. Fixed effects Bayesian network meta-analyses were performed to estimate the relative treatment effects for ADT + abiraterone vs ADT + docetaxel on overall survival (OS) and radiographic progression-free survival (rPFS). The high-volume disease subgroup of LATITUDE was used in the main analysis. The LATITUDE intention-to-treat population (newly diagnosed high-risk disease) was included as a sensitivity analysis. Since STAMPEDE [5] did not report a newly diagnosed high-risk/high-volume disease subgroup, its M1 population was included in a sensitivity analysis. The results for high-risk/high-volume disease suggested improvement with ADT + abiraterone vs ADT + docetaxel in OS (HR 0.84, 95%CI 0.63-1.14) and in rPFS (HR 0.73, 95%CI 0.57-0.94), with Bayesian probabilities for ADT + abiraterone 86.8% (OS) and 99.2% (rPFS) more effective. Furthermore, these results were consistent (albeit not statistically significant) across all sensitivity analyses.

The authors concluded that treatment with ADT + abiraterone resulted in greater reduction in risk of progression and death vs ADT + docetaxel. In the absence of head-to-head trials, indirect comparisons based on Bayesian network meta-analyses can provide useful insights to clinicians and reimbursement decision makers on the relative efficacy of treatment options for men with mHSPC.

Speaker: Susan Feyerabend, Studienpraxis Urologie, Nürtingen, Germany

Co-Authors: F. Saad (Montréal, Canada) T. Li (Raritan, United States of America) T. Ito (High Wycombe, United Kingdom) J. Diels (Beerse, Belgium) S. Van Sanden (Beerse, Belgium) P. De Porre (Beerse, Belgium) J. Roïz (London, United Kingdom) S. Abogunrin (London, United Kingdom) K. Fizazi (Villejuif, France)

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. Gravis G, Boher JM, Joly F, et al. Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial. Eur Urol. 2016;70(2):256-262.
2. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.
3. 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.
4. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.
5. 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.
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