Therapy of Advanced Prostate Cancer: Targeting the Androgen Receptor Axis in Earlier Lines of Treatment
With the decrease in PSA screening based on the 2011 United States Preventive Services Task Force guidelines and the potential approval of highly sensitive imaging techniques over the next few years, we are likely to see an increasing trend of metastatic prostate cancer diagnosis. Traditional therapy for nonmetastatic prostate cancer (nmPC) has consisted of androgen deprivation therapy (ADT) followed by other hormonal therapy maneuvers, such as anti-androgen withdrawal, herbal preparations, low dose steroids, or ketoconazole. Androgen receptor-axis-targeted therapies (ARAT) were previously only approved for patients with metastatic castration resistant prostate cancer (mCRPC). This has recently changed after reporting of results from the SPARTAN and PROSPER trials, which were conducted in nonmetastatic CRPC (nmCRPC) patients. These studies demonstrated improved metastasis-free survival with apalutamide and enzalutamide, each compared to placebo in a double blind randomized setting. In 2017, the LATITUDE and STAMPEDE studies demonstrated marked survival benefit with early abiraterone and prednisone in patients with metastatic hormone sensitive prostate cancer (mHSPC) in addition to ADT. Other second-generation AR antagonists are currently in phase 3 trials in mHSPC and nmCRPC. This article summarizes the key clinical trials that led to FDA approval of ARAT in the mHSPC and nmCRPC settings and highlights potential limitations, future directions, and treatment-algorithms when selecting patients for early therapy in mHSPC and NMPC.
Compliance with Ethical Standards
No external funding was used in the preparation of this manuscript.
Conflict of Interest
Dr. Ulka Vaishampayan declares research support and consulting for Astellas Inc. and honoraria from Pfizer Inc. and Bayer Inc. Dr. Harsh Shah declares that he has no conflicts of interest that might be relevant to the contents of this manuscript.
- 18.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.CrossRefGoogle Scholar
- 19.Gravis G, Boher JM, Joly F, Soulie M, Albiges L, Priou F, et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of meta- static burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol. 2016;70:256–62.CrossRefGoogle Scholar
- 28.Li T, Thompson M, Tran D. Metastatic-free survival and overall survival in prostate cancer [abstract]. Presented at: International Society for Pharmacoeconomics and Outcomes Research; 16–20 May 2015; Philadelphia, PA. Abstract PRM22.Google Scholar
- 29.Xie W, Sweeney C, Regan M, Nakabayashi M, Buyse M, Clarke N, et al. Metastasis free survival (MFS) is a surrogate for overall survival (OS) in localized prostate cancer (CaP). Ann Oncol. 2016;27(suppl 6):717O.Google Scholar
- 38.Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2016;17(6):747–56.CrossRefGoogle Scholar
- 39.Ryan CJ, Crawford ED, Shore ND, Underwood W 3rd, Taplin ME, Londhe A, et al. The IMAAGEN study: effect of abiraterone acetate and prednisone on prostate specific antigen and radiographic disease progression in patients with nonmetastatic castration resistant prostate cancer. J Urol. 2018;200(2):344–52.CrossRefGoogle Scholar