OBJECTIVES: To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available treatments for the management of metastatic hormone-sensitive prostate cancer (mHSPC), as there has been a paradigm shift with the use of next-generation androgen receptor inhibitors (ARIs) and docetaxel. METHODS: Multiple databases were searched for articles published before May 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis extension statement for network meta-analysis. Studies comparing overall/progression-free survival (OS/PFS) and/or adverse events (AEs) in patients with mHSPC were eligible. RESULTS: Nine studies (N = 9960) were selected, and formal network meta-analyses were conducted. Abiraterone (hazard ratio [HR] 0.83, 95% credible interval [CrI] 0.76-0.90), docetaxel (HR 0.90, 95% CrI 0.82-0.98), and enzalutamide (HR 0.85, 95% CrI 0.73-0.99) were associated with significantly better OS than androgen-deprivation therapy (ADT), and abiraterone emerged as the best option. Abiraterone (HR 0.71, 95% CrI 0.67-0.76), apalutamide (HR 0.73, 95% CrI 0.65-0.81), docetaxel (HR 0.84, 95% CrI 0.78-0.90), and enzalutamide (HR 0.67, 95% CrI 0.63-0.71) were associated with significantly better PFS than ADT, and enzalutamide emerged as the best option. Abiraterone (HR 0.85, 95% CrI 0.78-0.93), apalutamide (HR 0.87, 95% CrI 0.77-0.98), and enzalutamide (HR 0.80, 95% CrI 0.73-0.88) were significantly more effective than docetaxel. Regarding AEs, apalutamide was the likely best option among the three ARIs. In patients with low-volume mHSPC, enzalutamide was the best option in terms of OS and PFS. CONCLUSIONS: All three ARIs are effective therapies for mHSPC; apalutamide was the best tolerated. All three seemed more effective than docetaxel. These findings may facilitate individualised treatment strategies and inform future comparative trials.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology Medical University of Vienna Vienna Austria

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

Division of Urology Department of Special Surgery The University of Jordan Amman Jordan

European Association of Urology Research Foundation Arnhem Netherlands

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Research Center for Evidence Based Medicine Tabriz University of Medical Sciences Tabriz Iran

Zobrazit více v PubMed

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69: 7–34 PubMed

Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM. Increasing incidence of metastatic prostate cancer in the United States (2004–2013). Prostate Cancer Prostatic Dis 2016; 19: 395–7 PubMed

Bill‐Axelson A, Holmberg L, Garmo H et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med 2014; 370: 932–42 PubMed PMC

Walz J, Gallina A, Perrotte P et al. Clinicians are poor raters of life‐expectancy before radical prostatectomy or definitive radiotherapy for localized prostate cancer. BJU Int 2007; 100: 1254–8 PubMed

Shariat SF, Kattan MW, Vickers AJ, Karakiewicz PI, Scardino PT. Critical review of prostate cancer predictive tools. Future Oncol 2009; 5: 1555–84 PubMed PMC

Kluth LA, Shariat SF, Kratzik C et al. The hypothalamic‐pituitary‐gonadal axis and prostate cancer: implications for androgen deprivation therapy. World J Urol 2014; 32: 669–76 PubMed

Mottet N, Van den Bergh RC, Briers E. EAU guidelines: prostate cancer 2019. Eur Urol 2019; 76: 868–73 PubMed

Sweeney CJ, Chen YH, Carducci M et al. Chemohormonal therapy in metastatic hormone‐sensitive prostate cancer. N Engl J Med 2015; 373: 737–46 PubMed PMC

Fizazi K, Tran NP, Fein L et al. Abiraterone plus prednisone in metastatic, castration‐sensitive prostate cancer. N Engl J Med 2017; 377: 352–60 PubMed

Davis ID, Martin AJ, Stockler MR et al. Enzalutamide with standard first‐line therapy in metastatic prostate cancer. N Engl J Med 2019; 381: 121–31 PubMed

Armstrong AJ, Szmulewitz RZ, Petrylak DP et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone‐sensitive prostate cancer. J Clin Oncol 2019; 37: 2974–86 PubMed PMC

Chi KN, Agarwal N, Bjartell A et al. Apalutamide for Metastatic, castration‐sensitive prostate cancer. N Engl J Med 2019; 381: 13–24 PubMed

Kinsey EN, Zhang T, Armstrong AJ. Metastatic hormone‐sensitive prostate cancer. Cancer J 2020; 26: 64–75 PubMed

Wallis CJ, Klaassen Z, Bhindi B et al. Comparison of abiraterone acetate and docetaxel with androgen deprivation therapy in high‐risk and metastatic hormone‐naïve prostate cancer: a systematic review and network meta‐analysis. Eur Urol 2018; 73: 834–44 PubMed

Tan PS, Aguiar P Jr, Haaland B, Lopes G. Addition of abiraterone, docetaxel, bisphosphonate, celecoxib or combinations to androgen‐deprivation therapy (ADT) for metastatic hormone‐sensitive prostate cancer (mHSPC): a network meta‐analysis. Prostate Cancer Prostatic Dis 2018; 21: 516–23 PubMed

Marchioni M, Di Nicola M, Primiceri G et al. New antiandrogen compounds compared to docetaxel for metastatic hormone sensitive prostate cancer: results from a network meta‐analysis. J Urol 2020; 203: 751–9 PubMed

Sathianathen NJ, Koschel S, Thangasamy IA et al. Indirect comparisons of efficacy between combination approaches in metastatic hormone‐sensitive prostate cancer: a systematic review and network meta‐analysis. Eur Urol 2020; 77: 365–72 PubMed

Fizazi K, Tran NP, Fein L et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high‐risk metastatic castration‐sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double‐blind, phase 3 trial. Lancet Oncol 2019; 20: 686–700 PubMed

Clarke NW, Ali A, Ingleby FC et al. Addition of docetaxel to hormonal therapy in low‐ and high‐burden metastatic hormone sensitive prostate cancer: long‐term survival results from the STAMPEDE trial. Ann Oncol 2019; 30: 1992–2003 PubMed PMC

Hutton B, Salanti G, Caldwell DM et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta‐analyses of health care interventions: checklist and explanations. Ann Intern Med 2015; 162: 777–84 PubMed

Higgins JP, Altman DG, Gotzsche PC et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928 PubMed PMC

van Valkenhoef G, Lu G, de Brock B, Hillege H, Ades AE, Welton NJ. Automating network meta‐analysis. Res Synth Methods 2012; 3: 285–99 PubMed

Dias S, Welton NJ, Sutton AJ, Ades AE. NICE Decision Support Unit Technical Support Documents. NICE DSU Technical Support Document 2: A Generalised Linear Modelling Framework for Pairwise and Network Meta‐Analysis of Randomised Controlled Trials. London National Institute for Health and Care Excellence (NICE). Copyright © 2014 National Institute for Health and Clinical Excellence, unless otherwise stated. All rights reserved, 2014 PubMed

Woods BS, Hawkins N, Scott DA. Network meta‐analysis on the log‐hazard scale, combining count and hazard ratio statistics accounting for multi‐arm trials: a tutorial. BMC Med Res Methodol 2010; 10: 54 PubMed PMC

Rücker G, Schwarzer G. Ranking treatments in frequentist network meta‐analysis works without resampling methods. BMC Med Res Methodol 2015; 15: 58 PubMed PMC

Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple‐treatment meta‐analysis: an overview and tutorial. J Clin Epidemiol 2011; 64: 163–71 PubMed

Atkins D, Eccles M, Flottorp S et al. Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches the GRADE Working Group. BMC Health Serv Res 2004; 4: 38 PubMed PMC

Guyatt G, Oxman AD, Akl EA et al. GRADE guidelines: 1. Introduction‐GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64: 383–94 PubMed

Gravis G, Fizazi K, Joly F et al. Androgen‐deprivation therapy alone or with docetaxel in non‐castrate metastatic prostate cancer (GETUG‐AFU 15): a randomised, open‐label, phase 3 trial. Lancet Oncol 2013; 14: 149–58 PubMed

Gravis G, Boher J‐M, 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: 256–62 PubMed

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: 1163–77 PubMed PMC

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: 338–51 PubMed PMC

Kyriakopoulos CE, Chen YH, Carducci MA et al. Chemohormonal therapy in metastatic hormone‐sensitive prostate cancer: long‐term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol 2018; 36: 1080–7 PubMed PMC

Sydes MR, Spears MR, Mason MD et al. Adding abiraterone or docetaxel to long‐term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi‐arm, multi‐stage platform protocol. Ann Oncol 2018; 29: 1235–48 PubMed PMC

Hoyle AP, Ali A, James ND et al. Abiraterone in "high‐" and "low‐risk" metastatic hormone‐sensitive prostate cancer. Eur Urol 2019; 76: 719–28 PubMed

Feyerabend S, Saad F, Li T et al. Survival benefit, disease progression and quality‐of‐life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone‐sensitive prostate cancer: a network meta‐analysis. Eur J Cancer 2018; 103: 78–87 PubMed

Xie W, Regan MM, Buyse M et al. Metastasis‐free survival is a strong surrogate of overall survival in localized prostate cancer. J Clin Oncol 2017; 35: 3097–104 PubMed PMC

Morris MJ, Molina A, Small EJ et al. Radiographic progression‐free survival as a response biomarker in metastatic castration‐resistant prostate cancer: COU‐AA‐302 results. J Clin Oncol 2015; 33: 1356–63 PubMed PMC

Rathkopf DE, Beer TM, Loriot Y et al. Radiographic progression‐free survival as a clinically meaningful end point in metastatic castration‐resistant prostate cancer: the PREVAIL randomized clinical trial. JAMA Oncol 2018; 4: 694–701 PubMed PMC

Marco B, Martini A, Pfail J et al. Surrogate endpoints for overall survival for patients with metastatic hormone‐sensitive prostate cancer in the CHAARTED trial. Eur Urol Open Sci 2020; 20: S142 PubMed

Schmitt B, Bennett C, Seidenfeld J, Samson D, Wilt T. Maximal androgen blockade for advanced prostate cancer. Cochrane Database Syst Rev 2000; 2: CD001526 PubMed PMC

Clegg NJ, Wongvipat J, Joseph JD et al. ARN‐509: a novel antiandrogen for prostate cancer treatment. Can Res 2012; 72: 1494–503 PubMed PMC

Nelson PS. Molecular states underlying androgen receptor activation: a framework for therapeutics targeting androgen signaling in prostate cancer. J Clin Oncol 2012; 30: 644–6 PubMed

Morgans AK, Chen YH, Sweeney CJ et al. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer. J Clin Oncol 2018; 36: 1088–95 PubMed PMC

Chi KN, Protheroe A, Rodríguez‐Antolín A et al. Patient‐reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration‐naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol 2018; 19: 194–206 PubMed

Stenzl A, Dunshee C, De Giorgi U et al. Effect of enzalutamide plus androgen deprivation therapy on health‐related quality of life in patients with metastatic hormone‐sensitive prostate cancer: an analysis of the ARCHES randomised, placebo‐controlled, phase 3 study. Eur Urol 2020; 78: 603–14 PubMed

Agarwal N, McQuarrie K, Bjartell A et al. Health‐related quality of life after apalutamide treatment in patients with metastatic castration‐sensitive prostate cancer (TITAN): a randomised, placebo‐controlled, phase 3 study. Lancet Oncol 2019; 20: 1518–30 PubMed

Rush HL, Cook AD, Brawley CD et al. Comparative quality of life in patients randomized contemporaneously to docetaxel or abiraterone in the STAMPEDE trial. J Clin Oncol 2020; 38: 14.

Sathianathen NJ, Alarid‐Escudero F, Kuntz KM et al. A cost‐effectiveness analysis of systemic therapy for metastatic hormone‐sensitive prostate cancer. Eur Urol Oncol 2019; 2: 649–55 PubMed

Chiang CL, So TH, Lam TC, Choi HC. Cost‐effectiveness analysis of Abiraterone Acetate versus Docetaxel in the management of metastatic castration‐sensitive prostate cancer: Hong Kong's perspective. Prostate Cancer Prostatic Dis 2020; 23: 108–15 PubMed

Aguiar PN Jr, Tan PS, Simko S et al. Cost‐effectiveness analysis of abiraterone, docetaxel or placebo plus androgen deprivation therapy for hormone‐sensitive advanced prostate cancer. Einstein (São Paulo) 2019; 17: eGS4414. PubMed PMC

Riaz IB, Almutairi A, Lang DK et al. Cost‐effectiveness of novel antiandrogens (AAs) for treatment of nonmetastatic castrate‐resistant prostate cancer (nmCRPC). J Clin Oncol 2020; 38: 5583.

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