Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study

Eur Urol. 2020 Oct;78(4):603-614. doi: 10.1016/j.eururo.2020.03.019. Epub 2020 Apr 23.


Background: In the ARCHES study in metastatic hormone-sensitive prostate cancer (mHSPC), enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) versus ADT alone.

Objective: To evaluate patient-reported outcomes (PROs) to week 73.

Design, setting, and participants: ARCHES (NCT02677896) was a randomised, double-blind, placebo-controlled, phase 3 study in mHSPC patients.

Intervention: Enzalutamide (160 mg/day) plus ADT or placebo plus ADT.

Outcome measurements and statistical analysis: PROs were assessed at baseline, week 13, and every 12 wk until disease progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate 25 (QLQ-PR25), Functional Assessment of Cancer Therapy-Prostate (FACT-P), Brief Pain Inventory Short Form, and EuroQoL 5-Dimensions, 5-Levels (EQ-5D-5 L) instruments. Endpoints included time to first (TTFD) and first confirmed (TTFCD) clinically meaningful deterioration (using predefined questionnaire thresholds) in health-related quality of life (HRQoL) and pain.

Results and limitations: A total of 1150 patients received ADT plus enzalutamide (n = 574) or placebo (n = 576). Baseline PRO scores indicated high HRQoL and low pain, which was generally maintained in both groups. There were no statistically significant (nominal p > 0.05) between-group differences that occurred in both TTFD and TTFCD together for QLQ-PR25 and FACT-P scores. Enzalutamide significantly delayed TTFD in worst pain (by ∼3 mo; nominal p = 0.032), pain severity (nominal p = 0.021), and EQ-5D-5 L visual analogue scale score (nominal p = 0.0070) versus placebo (not significant for confirmed deterioration for pain outcomes). Enzalutamide delays deterioration in several HRQoL subscales and pain severity in high-volume disease.

Conclusions: Enzalutamide plus ADT enables men with mHSPC to maintain high-functioning HRQoL and low symptom burden.

Patient summary: This study examined the effect on health-related quality of life and pain of adding enzalutamide or placebo to androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer. Addition of enzalutamide allowed patients to maintain their health-related quality of life.

Keywords: ARCHES; Enzalutamide; Metastatic hormone-sensitive; Pain; Patient-reported outcomes; Prostate cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Androgen Antagonists / therapeutic use*
  • Benzamides / therapeutic use*
  • Combined Modality Therapy
  • Gonadotropin-Releasing Hormone / agonists*
  • Humans
  • Male
  • Neoplasm Metastasis
  • Nitriles / therapeutic use*
  • Patient Reported Outcome Measures*
  • Phenylthiohydantoin / therapeutic use*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Quality of Life*
  • Time Factors


  • Androgen Antagonists
  • Benzamides
  • Nitriles
  • Phenylthiohydantoin
  • Gonadotropin-Releasing Hormone
  • enzalutamide

Associated data

  • ClinicalTrials.gov/NCT02677896