Enzalutamide Plus ADT Reduces Death Risk in Hormone-Sensitive Prostate Cancer

Adding enzalutamide to androgen deprivation therapy (ADT) significantly reduced the risk for metastatic progression or death in men with metastatic hormone-sensitive prostate cancer (HSPC), according to results from the ARCHES trial (J Clin Oncol. 2019 Jul 22. Epub ahead of print).

ARCHES Clinical Trial

 “Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer,” explained Andrew J. Armstrong, MD, ScM, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, and colleagues, who conducted the multi-national ARCHES study to examine the safety and efficacy of using this drug in patients with metastatic HSPC.

The double-blind, phase 3 trial included 1150 men with metastatic HSPC who were randomized in a 1:1 ratio to receive enzalutamide 160 mg daily or placebo plus ADT. The primary end point of the study was radiographic progression-free survival (PFS).

Reduced Death Risk, Improved Quality of Life

The risk for radiographic progression or death was reduced significantly with enzalutamide plus ADT compared with placebo plus ADT as of October 14, 2018 (hazard ratio, 0.39; 95% CI, 0.30-0.50; P <.001; median, not reached vs 19.0 months). The investigators observed similar significant improvements in radiographic PFS in prespecified groups divided based on disease volume and previous docetaxel therapy.

In addition, significant decreases in risk for prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and pain progression were seen with the addition of enzalutamide to ADT. Findings also demonstrated that more patients achieved an undetectable prostate-specific antigen level and/or objective response with enzalutamide plus ADT than with placebo plus ADT (P<.001).

High quality of life was reported at baseline in both therapy arms and maintained over time. Adverse events of grade ≥3 were reported in 24.3% and 25.6% of patients in the enzalutamide plus ADT versus placebo plus ADT arms, respectively, with no unexpected adverse events.

Promising Results With Enzalutamide Plus ADT

“Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer,” Dr Armstrong and colleagues determined.

For more information about this study, listen to Oncology Learning Network’s interview with Dr Armstrong, “Enzalutamide–ADT Combo significantly Improves PFS in Metastatic Hormone-Sensitive Prostate Cancer,” in which he discusses the clinical significance of the ARCHES trial and its findings.—Hina Porcelli