ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer.

Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC).

ARCHES ( identifier: NCT02677896 ) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival.

As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT (P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events.

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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 Jul 22 [Epub ahead of print]

Andrew J Armstrong, Russell Z Szmulewitz, Daniel P Petrylak, Jeffrey Holzbeierlein, Arnauld Villers, Arun Azad, Antonio Alcaraz, Boris Alekseev, Taro Iguchi, Neal D Shore, Brad Rosbrook, Jennifer Sugg, Benoit Baron, Lucy Chen, Arnulf Stenzl

1 Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC., 2 The University of Chicago, Chicago, IL., 3 Yale Cancer Center, New Haven, CT., 4 The University of Kansas Medical Center, Kansas City, KS., 5 Lille University, Lille, France., 6 Monash Health, Melbourne, Victoria, Australia., 7 Hospital Clinic of Barcelona, Barcelona, Spain., 8 Hertzen Moscow Cancer Research Institute, Moscow, Russia., 9 Osaka City University Graduate School of Medicine, Osaka, Japan., 10 Carolina Urologic Research Center, Myrtle Beach, SC., 11 Pfizer, San Diego, CA., 12 Astellas Pharma, Northbrook, IL., 13 Astellas Pharma, Leiden, the Netherlands., 14 Eberhard Karls University of Tübingen, Tübingen, Germany.