Enzalutamide Provides Similar Clinical Benefit in Men With Metastatic Hormone-Sensitive Prostate Cancer With Either De Novo Disease or Disease Progression

By Hiten D. Patel, MD, MPH - December 14, 2021

The addition of enzalutamide, a second-generation, nonsteroidal androgen-receptor inhibitor, to standard androgen deprivation therapy (ADT) was shown to improve progression-free survival (PFS) for men with metastatic hormone-sensitive prostate cancer (mHSPC) in the phase 3 ARCHES trial. These results formed the basis for the FDA’s approval of enzalutamide for the treatment of patients with mHSPC in December 2019.

In the ARCHES trial, many patients may have had mHSPC with de novo distant metastasis (stage M1) at the time of diagnosis, while others may have initially had no distant metastasis (stage M0), but it developed over time. Dr. Arun Azad (Monash Health, Melbourne, Australia) and ARCHES co-investigators reported that these two groups of patients derived similar benefit in PFS from the addition of enzalutamide in a poster presented during the 2021 ASCO Genitourinary Cancers Symposium.

Among the 1136 patients evaluated in the original ARCHES trial, 246 (21.7%) initially had M0 disease and later progressed to mHSPC. The investigators noted that the de novo M1 patients had higher volume disease and higher prior docetaxel use compared to the initial M0 patients. However, the benefit due to enzalutamide was similar in both groups with statistically significant improvements in progress-free survival (hazard ratio [HR] for initially M0, 0.42; HR for de novo M1, 0.38). The study concluded that the results of this post hoc analysis support the clinical benefit of combination enzalutamide and androgen deprivation therapy among both subgroups of patients with mHSPC.


Hiten D. Patel, MD, MPH, completed residency training in urologic surgery at the James Buchanan Brady Urological Institute and is currently a Clinical Instructor and Fellow in Urologic Oncology at Loyola University Medical Center. He has published studies related to epidemiology, comparative effectiveness, evidence-based reviews, and clinical trials in urologic oncology and related fields.



Azad A, Villers A, Alekseev B, et al. Efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) in men with de novo (M1) metastatic hormone-sensitive prostate cancer (mHSPC) versus progression to mHSPC (M0): Post hoc analysis of the phase III ARCHES trial. J Clin Oncol. 2021;39(6, suppl):27. Abstract 102. doi: 10.1200/JCO.2021.39.6_ suppl.102

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(32):2974-2986. doi: 10.1200/ JCO.19.00799

US Food & Drug Administration (FDA). FDA approves enzalutamide for metastatic castration- sensitive prostate cancer. December 17, 2019. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-enzalutamide-metastatic-castration-sensitive-prostate-cancer