Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer

Author(s): Andrew J. Armstrong , MD, ScM1; Arun A. Azad , MBBS, PhD2,3; Taro Iguchi , MD, PhD4; Russell Z. Szmulewitz, MD5; Daniel P. Petrylak , MD6; Jeffrey Holzbeierlein, MD7; Arnauld Villers , MD8; Antonio Alcaraz , MD, PhD9; Boris Alekseev, MD10; Neal D. Shore , MD11; Francisco Gomez-Veiga, MD, PhD12,13; Brad Rosbrook, MS14; Fabian Zohren, MD, PhD14; Shunsuke Yamada, MEng15; Gabriel P. Haas, MD15; and Arnulf Stenzl, MD16
Source: DOI: 10.1200/JCO.22.00193 Journal of Clinical Oncology 40, no. 15 (May 20, 2022) 1616-1622.
Lucio Gordan MD

Important clinical trial update with more mature data. Risk of death is 34% lower in combined enzalutamide and LHRH analog versus the latter alone.

In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature. In the phase III, double-blind, global ARCHES trial ( identifier: NCT02677896), 1,150 patients with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg once daily) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use. Here, we report the final prespecified analysis of overall survival (key secondary end point) and an update on rPFS, other secondary end points, and safety. After unblinding, 180 (31.3%) progression-free patients randomly assigned to placebo plus ADT crossed over to open-label enzalutamide plus ADT. As of May 28, 2021 (median follow-up, 44.6 months), 154 of 574 patients randomly assigned to enzalutamide plus ADT and 202 of 576 patients randomly assigned to placebo plus ADT had died. Enzalutamide plus ADT reduced risk of death by 34% versus placebo plus ADT (median not reached in either group; hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P < .001). Enzalutamide plus ADT continued to improve rPFS and other secondary end points. Adverse events were generally consistent with previous reports of long-term enzalutamide use. In conclusion, enzalutamide plus ADT significantly prolongs survival versus placebo plus ADT in patients with mHSPC.

Author Affiliations

1Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University, Durham, NC 2Peter MacCallum Cancer Center, Melbourne, Victoria, Australia 3Monash Health, Melbourne, Victoria, Australia 4Kanazawa Medical University, Ishikawa, Japan 5The University of Chicago, Chicago, IL 6Yale Cancer Center, New Haven, CT 7The University of Kansas Medical Center, Kansas City, KS 8University Hospital Centre, Lille University, Lille, France 9Hospital Clinic de Barcelona, Barcelona, Spain 10Hertzen Moscow Cancer Research Institute, Moscow, Russia 11Carolina Urologic Research Center, Myrtle Beach, SC 12Hospital Universitario de Salamanca, GITUR-IBSAL, Salamanca, Spain 13Complexo Hospitalario Universitario de A Coruña, Coruña, Spain 14Pfizer Inc, New York, NY 15Astellas Pharma Inc, Northbrook, IL 16University Hospital, Eberhard Karls University of Tübingen, Tübingen, Germany

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