Combining enzalutamide with androgen deprivation therapy (ADT) provides a long-term survival benefit, when compared with ADT alone, in patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to final results from the phase 3 ARCHES trial.1

These results were presented at the European Society for Medical Oncology (ESMO) Congress 2021 by Andrew J. Armstrong, MD, of the Duke Cancer Institute Center for Prostate & Urologic Cancers in Durham, North Carolina.

Dr Armstrong noted that enzalutamide plus ADT was approved for the treatment of mHSPC in the United States and Europe based on prior results from the ARCHES trial ( Identifier: NCT02677896).

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The phase 3 trial enrolled 1150 men with mHSPC. They were randomly assigned 1:1 to receive enzalutamide plus ADT (574 patients) or placebo plus ADT (576 patients) and were stratified by disease volume and previous docetaxel treatment.

In the primary analysis, enzalutamide plus ADT reduced the risk of radiographic disease progression by 61% (P <.001) and improved key secondary endpoints, but overall survival (OS) data were immature at that time.2

Based on results of the primary analysis, the study was unblinded to allow for crossover. A total of 180 patients (31.3%) in the placebo arm crossed over to receive enzalutamide plus ADT. The median time to crossover was 21.5 months.

At ESMO 2021, Dr Armstrong reported results as of May 28, 2021. At that point, there were 356 deaths — 154 in the enzalutamide arm and 202 in the placebo arm.

The median follow-up was 44.6 months. The median treatment duration was 40.2 in the enzalutamide arm, 13.8 months in the placebo arm, and 23.9 months for the crossover patients.

Dr Armstrong reported that patients in the enzalutamide arm had a significant delay in the need for subsequent antineoplastic therapy. The median time to subsequent treatment was not reached in the enzalutamide arm and was 40.5 months in the placebo arm (hazard ratio [HR], 0.38; 95% CI, 0.31-0.48).

The median OS was not reached in either arm, but enzalutamide plus ADT significantly improved OS by 34% compared with placebo plus ADT (HR, 0.66; 95% CI, 0.53-0.81; P <.0001). At 4 years, the OS rate was 71% in the enzalutamide arm and 57% in the placebo arm.

The OS benefit with enzalutamide was maintained regardless of disease volume, prior local therapy, disease localization, Gleason score, baseline prostate-specific antigen level, functional status, age, and geography.

“The survival benefit does not appear to be related to a differential receipt of subsequent antineoplastic therapies, and the survival benefit was observed despite 70% of placebo patients receiving life-prolonging therapy to date…, including 40% who received enzalutamide,” Dr Armstrong said.

He added that the safety results of the final analysis are consistent with results from the primary analysis.

There were no fatal treatment-related adverse events (AE) in the enzalutamide arm, but there was 1 in the placebo arm. More patients in the enzalutamide arm than in the placebo arm had to stop study treatment due to AEs — 13.8% and 5.6%, respectively.

Disclosures: This research was supported by Astellas Pharma and Pfizer. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. Armstrong AJ, Iguchi T, Azad AA, et al. Final overall survival (OS) analysis from ARCHES: A phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC). Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract LBA25.
  2. 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

This article originally appeared on Cancer Therapy Advisor