Systemic Therapies for Metastatic Hormone-Sensitive Prostate Cancer: Network Meta-Analysis.

Abstract

OBJECTIVES\nManagement of metastatic hormone-sensitive prostate cancer (mHSPC) has undergone a paradigm shift with the use of next-generation androgen receptor inhibitors (ARIs) and docetaxel. However, direct comparative data are not available to inform treatment decisions and/or recommendations. We performed a systematic review and network meta-analysis to indirectly compare the efficacy and safety of currently available treatments.\n\n\nMETHODS\nMultiple 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.\n\n\nRESULTS\nNine studies (n=9,960) 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. With regard to 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.\n\n\nCONCLUSIONS\nAll three ARIs are effective therapies for mHSPC; apalutamide was the best tolerated. All three seemed more effective than docetaxel. These findings may facilitate individualized treatment strategies and inform future comparative trials.