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

Andrew J. Armstrong, MD, ScM; Arun A. Azad, MBBS, PhD; Taro Iguchi, MD, PhD; Russell Z. Szmulewitz, MD; Daniel P. Petrylak, MD; Jeffrey Holzbeierlein, MD; Arnauld Villers, MD; Antonio Alcaraz, MD, PhD; Boris Alekseev, MD; Neal D. Shore, MD; Francisco Gomez-Veiga, MD, PhD; Brad Rosbrook, M; Fabian Zohren, MD, PhD; Shunsuke Yamada, MEng; Gabriel P. Haas, MD; Arnulf Stenzl, MD

Disclosures

J Clin Oncol. 2022;40(15):1616-1622. 

In This Article

Abstract and Introduction

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

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 (ClinicalTrials.gov 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.

Introduction

Enzalutamide in combination with androgen deprivation therapy (ADT) is approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC [also referred to as metastatic castration-sensitive prostate cancer])[1,2] on the basis of proven clinical benefits in the phase III ARCHES trial (ClinicalTrials.gov identifier: NCT02677896). At the time of the primary analysis, enzalutamide plus ADT significantly reduced the risk of radiographic disease progression or death in men with mHSPC; however, overall survival (OS) data were considered immature.[3]

Herein, we report the final prespecified OS analysis and an update on radiographic progression-free survival (rPFS), other secondary end points, and safety.

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