title: Impact of enzalutamide on quality of life in men with metastatic castration-resistant prostate cancer after chemotherapy: additional analyses from the AFFIRM randomized clinical trial.
abstract: BACKGROUND
  To present longitudinal changes in Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores during 25-week treatment with enzalutamide or placebo in men with progressive metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy in the AFFIRM trial.
  
  
  METHODS
  Patients were randomly assigned to enzalutamide 160 mg/day or placebo. FACT-P was completed before randomization, at weeks 13, 17, 21, and 25, and every 12 weeks thereafter while on study treatment. Longitudinal changes in FACT-P scores from baseline to 25 weeks were analyzed using a mixed effects model for repeated measures (MMRM), with a pattern mixture model (PMM) applied as secondary analysis to address non-ignorable missing data. Cumulative distribution function (CDF) plots were generated and different methodological approaches and models for handling missing data were applied. Due to the exploratory nature of the analyses, adjustments for multiple comparisons were not made. AFFIRM is registered with ClinicalTrials.gov, number NCT00974311.
  
  
  RESULTS
  The intention-to-treat FACT-P population included 938 patients (enzalutamide, n = 674; placebo n = 264) with evaluable FACT-P assessments at baseline and ≥1 post-baseline assessment. After 25 weeks, the mean FACT-P total score decreased by 1.52 points with enzalutamide compared with 13.73 points with placebo (P < 0.001). In addition, significant treatment differences at week 25 favoring enzalutamide were evident for all FACT-P subscales and indices, whether analyzed by MMRM or PMM. CDF plots revealed differences favoring enzalutamide compared with placebo across the full range of possible response levels for FACT-P total and all disease- and symptom-specific subscales/indices.
  
  
  CONCLUSIONS
  In men with progressive mCRPC after docetaxel-based chemotherapy, enzalutamide is superior to placebo in health-related quality-of-life outcomes, regardless of analysis model or threshold selected for meaningful response.
  
  
  BACKGROUND
  NCT00974311.
authors.affiliation: Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA. Electronic address: d-cella@northwestern.edu.
authors.forename: D
authors.initials: D
authors.lastname: Cella
authors.affiliation: Consulting, Quintiles, Hoofddorp.
authors.forename: C
authors.initials: C
authors.lastname: Ivanescu
authors.affiliation: Global Data Science, Health Economics & Outcomes Research, Astellas Pharma Global Development, Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Holmstrom
authors.affiliation: Health Economics & Clinical Outcomes Research, Astellas Pharma US, Inc., Northbrook, USA.
authors.forename: C N
authors.initials: CN
authors.lastname: Bui
authors.affiliation: Health Economics & Clinical Outcomes Research, Astellas Pharma US, Inc., Northbrook, USA.
authors.forename: J
authors.initials: J
authors.lastname: Spalding
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos / Q000008:administration & dosage; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011788:Quality of Life; D057566:Self Report; D011795:Surveys and Questionnaires; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: health-related quality of life; metastatic castration-resistant prostate cancer; patient-reported outcomes