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

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 (Clinical-Trials. gov, NCT01288911). Patients were randomised (1:1) via an interactive voice and web response system to enzalutamide 160 mg/d (n = 184) or bicalutamide 50 mg/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. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.