title: 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: Improving health-related quality of life (HRQoL) is an important goal in metastatic castration-resistant prostate cancer (mCRPC).
  
  
  
  To examine the impact of enzalutamide versus bicalutamide on HRQoL in mCRPC.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  In patients with asymptomatic/mildly symptomatic mCRPC, enzalutamide provides HRQoL benefit versus bicalutamide.
  
  
  
  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: Department of Urology, Cologne University, Cologne, Germany. Electronic address: axel.heidenreich@uk-koeln.de.
authors: Axel
authors: A
authors: Heidenreich
authors: Department of Urology, Guy's, King's, and St Thomas' Hospital, London, UK.
authors: Simon
authors: S
authors: Chowdhury
authors: Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
authors: Laurence
authors: L
authors: Klotz
authors: Centre for Applied Urological Research, Queen's University, Kingston, ON, Canada.
authors: David Robert
authors: DR
authors: Siemens
authors: Department of Urology, Lille University Medical Center, Lille University, Lille, France.
authors: Arnauld
authors: A
authors: Villers
authors: Quintiles Advisory Services, Hoofddorp, the Netherlands.
authors: Cristina
authors: C
authors: Ivanescu
authors: Astellas Pharma Inc., Leiden, The Netherlands.
authors: Stefan
authors: S
authors: Holmstrom
authors: Astellas Pharma Inc., Leiden, The Netherlands.
authors: Benoit
authors: B
authors: Baron
authors: Medivation Inc., San Francisco, CA, USA.
authors: Fong
authors: F
authors: Wang
authors: Medivation Inc., San Francisco, CA, USA.
authors: Ping
authors: P
authors: Lin
authors: Carolina Urologic Research Centre, Myrtle Beach, SC, USA.
authors: Neal D
authors: ND
authors: Shore
mesh_terms: D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D000072716:Cancer Pain / Q000209:etiology; D002277:Carcinoma / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009570:Nitriles / Q000627:therapeutic use*; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D014105:Tosyl Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D014105:Tosyl Compounds; D010669:Phenylthiohydantoin; C540278:enzalutamide; C053541:bicalutamide
keywords: Bicalutamide; Enzalutamide; Metastatic castration-resistant prostate cancer; Quality of life