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.

Abstract

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.

• Authors: Arnulf Stenzl, Curtis Dunshee, Ugo De Giorgi, Boris Alekseev, Taro Iguchi, Russell Z Szmulewitz, Thomas W Flaig, Bertrand Tombal, Robert Morlock, Cristina Ivanescu, Krishnan Ramaswamy, Fred Saad, Andrew J Armstrong
• Journal: European urology (Eur Urol) Vol. 78 Issue 4 Pg. 603-614 (10 2020) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 32336645 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

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

Topics

• Adenocarcinoma (drug therapy, 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, pathology)
• Quality of Life
• Time Factors