Abstract
Purpose of Review
Androgen deprivation therapy (ADT) has been the standard-of-care (SOC) for metastatic hormone-sensitive prostate cancer (mHSPC) since the middle of the twentieth century. Recently, several practice-changing trials have added new therapy options for these patients. Here we review these studies and discuss guidelines on treatment decision-making.
Recent Findings
A trio of studies (GETUG-AFU15, STAMPEDE, CHAARTED) combining docetaxel chemotherapy with ADT all showed clinical benefit of the addition. More recently, the LATITUDE and STAMPEDE-Abiraterone studies established yet another new option for up-front treatment of newly diagnosed metastatic prostate cancer, showing significantly prolonged overall survival (OS) and progression-free survival (PFS) compared to ADT alone in men with high-risk mHSPC.
Summary
With the recent demonstration that adding either docetaxel or abiraterone plus prednisone to ADT significantly improves survival in mHSPC, physicians are confronted by a growing body of clinical data and treatment regimens. Men with high-volume and/or high-risk metastatic disease should not be treated with ADT alone without strong consideration of docetaxel or abiraterone. The choice of a first-line therapy should be made based on risk stratification, patients’ comorbidities, toxicities, quality-of-life (QOL) considerations, and cost.
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References
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Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.
•• Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46. The CHAARTED trial looked at a total of 790 patients with mHSPC randomized to ADT vs ADT + docetaxel without prednisone. This showed a significant improvement in clinical outcomes with the addition of docetaxel. The majority of the benefit, however, was seen in the high volume/high risk patients.
•• James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, 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. This is a multi-arm, multi-stage study run primarily in the UK comparing ADT vs ADT + docetaxel with prednisolone. This helped confirm clinical benefit of the addition of docetaxel to uprfront ADT.
•• James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338–51. This study encompasses additional arms of the STAMPEDE trial comparing ADT vs ADT + abiraterone/prednisone. Clinical benefit was seen with the addition of abiraterone, and this trial included N0M0 patients as well.
•• Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60. This is a double blinded, placebo controlled, randomized trial comparing ADT + placebo to ADT + abiraterone/prednisone in metastatic prostate cancer patients (n=1199). It showed clinical benefit of adding abiraterone/prednisone across all subgroups.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.
Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, 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.
• Gravis G, 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;0:256–62. This study reports a randomized trial of ADT vs ADT + docetaxel in mHSPC (n=385). It showed an improvement in progression free survival, but not overall survival with the addition of docetaxel.
Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, 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.
Vale CL, Burdett S, Rydzewska LHM, Albiges L, Clarke NW, Fisher D, et al. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol. 2016;17:243–56.
Fizazi K, Jenkins C, Tannock IF. Should docetaxel be standard of care for patients with metastatic hormone-sensitive prostate cancer? Pro and contra. Ann Oncol. 2015;26:1660–7.
Rayner LJA, Challapalli A, Blackmore E, Rea K, Wells N, White P, et al. Upfront docetaxel with androgen deprivation therapy in the elderly patient with metastatic hormone-naïve prostate cancer: single institution experience. J Clin Oncol. 2018;36:328.
Morris MJ, Rumble RB, Basch E, Hotte SJ, Loblaw A, Rathkopf D, et al. Optimizing anticancer therapy in metastatic non-castrate prostate cancer: American society of clinical oncology clinical practice guideline. J Clin Oncol. 2018;36:1521–39.
Hurwitz MD, Harris J, Sartor O, **ao Y, Shayegan B, Sperduto PW, et al. Adjuvant radiation therapy, androgen deprivation, and docetaxel for high-risk prostate cancer postprostatectomy: results of NRG oncology/RTOG study 0621. Cancer. 2017;123:2489–96.
de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.
Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13:983–92.
Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.
Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152–60.
Wallis CJD, et al. Comparison of abiraterone acetate and docetaxel with androgen deprivation therapy in high-risk and metastatic hormone-naive prostate cancer: a systematic review and network meta-analysis. Eur Urol. 2017;73:834–844.
Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, et al. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34:1652–9.
Pollard ME, Moskowitz AJ, Diefenbach MA, Hall SJ. Cost-effectiveness analysis of treatments for metastatic castration resistant prostate cancer. Asian J Urol. 2017;4:37–43.
Poon DMC, Chan K, Lee SH, Chan TW, Sze H, Lee EKC, et al. Differences in clinical outcome between docetaxel and abiraterone acetate as the first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer patients with or without the ineligible clinical factors of the COU-AA-302 study. Prostate Int. 2018;6:24–30.
Patrick-Miller LJ, Chen YH, Carducci MA, Cella D, DiPaola RS, Gartrell BA, et al. Quality of life (QOL) analysis from E3805, chemohormonal androgen ablation randomized trial (CHAARTED) in prostate cancer (PrCa). J Clin Oncol. 2016;34:286.
Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, 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.
Lavaud P, Gravis G, Foulon S, Joly F, Oudard S, Priou F, et al. Anticancer activity and tolerance of treatments received beyond progression in men treated upfront with androgen deprivation therapy with or without docetaxel for metastatic castration-naive prostate cancer in the GETUG-AFU 15 phase 3 trial. Eur Urol. 2018;73:696–703.
Robinson D, van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;162:454.
Taplin M, et al. Clinical factors associated with AR-V7 detection in ARMOR3-SV, a randomized trial of galeterone (Gal) vs enzalutamide (Enz) in men with AR-V7+ metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2017;35:5005.
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Lai Xu declares no potential conflicts of interest.
Russell K. Pachynski reports speakers’ bureau and advisory boards for Sanofi, unrelated research collaboration with Janssen.
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This article is part of the Topical Collection on Prostate Cancer
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Xu, L., Pachynski, R.K. Contemporary Management of the Newly Diagnosed Prostate Cancer Patient with Metastatic Disease at Presentation. Curr Urol Rep 19, 79 (2018). https://doi.org/10.1007/s11934-018-0835-7
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DOI: https://doi.org/10.1007/s11934-018-0835-7