Impact of Enzalutamide Compared with Bicalutamide on Quality of Life in Men with Metastatic Castration-resistant Prostate Cancer: Additional Analyses from the TERRAIN Randomised Clinical Trial.

Abstract

BACKGROUND:

Improving health-related quality of life (HRQoL) is an important goal in metastatic castration-resistant prostate cancer (mCRPC).

OBJECTIVE:

To examine the impact of enzalutamide versus bicalutamide on HRQoL in mCRPC.

DESIGN, SETTING, AND PARTICIPANTS:

TERRAIN is a multinational, phase 2, randomised, double-blind study in asymptomatic/mildly symptomatic men with mCRPC (ClinicalTrials.gov, NCT01288911). Patients were randomised (1:1) via an interactive voice and web response system to enzalutamide 160mg/d (n=184) or bicalutamide 50mg/d (n=191), with androgen deprivation therapy.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

HRQoL was assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P), European Quality of Life 5-Domain Scale (EQ-5D), and Brief Pain Inventory, Short-form questionnaires every 12 wk. Primary and secondary analyses utilised mixed models for repeated measures and pattern mixture models, respectively.

RESULTS AND LIMITATIONS:

At 61 wk, 84 (46%) enzalutamide and 39 (20%) bicalutamide patients in the study were assessed. At 61 wk, changes from baseline favoured enzalutamide versus bicalutamide on three FACT-P domains in mixed models for repeated measures analyses and seven in pattern mixture models analyses. There were no differences in changes for EQ-5D index/visual analogue scale scores. Risk of first deterioration was lower with enzalutamide for FACT-P total (hazard ratio: 0.64, 95% confidence interval: 0.46-0.89, p=0.007), FACT-G total (hazard ratio: 0.70, 95% confidence interval: 0.50-0.98, p=0.04), PCS pain (hazard ratio: 0.74, 95% confidence interval: 0.54-1.00, p=0.048), and EQ-5D index (hazard ratio: 0.66, 95% confidence interval: 0.47-0.93, p=0.02) scores versus bicalutamide. Brief Pain Inventory, Short-form scores increased in both groups. There was no difference in time-to-pain progression. Study limitations include the exploratory nature of the HRQoL analyses, lack of multiple comparisons corrections, and unknown effects of anxiety/depression on HRQoL.

CONCLUSIONS:

In patients with asymptomatic/mildly symptomatic mCRPC, enzalutamide provides HRQoL benefit versus bicalutamide.

PATIENT SUMMARY:

Enzalutamide treatment was associated with better health-related quality of life in several domains versus bicalutamide in asymptomatic/mildly symptomatic metastatic castration-resistant prostate cancer. This likely relates to previously reported lower rates of symptomatic disease progression.

• Authors: Axel Heidenreich, Simon Chowdhury, Laurence Klotz, David Robert Siemens, Arnauld Villers, Cristina Ivanescu, Stefan Holmstrom, Benoit Baron, Fong Wang, Ping Lin, Neal D Shore
• Journal: European urology (Eur Urol) Vol. 71 Issue 4 Pg. 534-542 (04 2017) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 27497762 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anilides
• Antineoplastic Agents
• Benzamides
• Nitriles
• Tosyl Compounds
• Phenylthiohydantoin
• enzalutamide
• bicalutamide

Topics

• Anilides (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Benzamides
• Cancer Pain (etiology)
• Carcinoma (complications, drug therapy, secondary)
• Double-Blind Method
• Humans
• Male
• Neoplasm Metastasis
• Nitriles (therapeutic use)
• Phenylthiohydantoin (analogs & derivatives, therapeutic use)
• Proportional Hazards Models
• Prostatic Neoplasms, Castration-Resistant (complications, drug therapy, pathology)
• Quality of Life
• Tosyl Compounds (therapeutic use)
• Treatment Outcome