title: Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials.
abstract: We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo.
  
  
  
  Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments.
  
  
  
  First SREs caused HRQoL deterioration in both trials. Spinal cord compression had the largest impact, with clinically meaningful reductions in seven of nine FACT-P domains in PREVAIL and all three in AFFIRM (mean (95% confidence interval (CI)) change in FACT-P total score -16.95 (-26.47, -7.44) and -9.69 (-16.10, -3.27), respectively). In PREVAIL, first SREs caused clinically meaningful declines in EQ-5D utility index, irrespective of category; spinal cord compression had the largest impact (mean (95% CI) change -0.24 (-0.39, -0.08)). In AFFIRM, FACT-P and FACT-General total scores showed clinically meaningful declines after radiation/surgery to bone.
  
  
  
  SREs were associated with clinically meaningful functional declines in the daily lives of patients with mCRPC. Spinal cord compression had the largest impact on HRQoL.
authors.affiliation: Prostate Cancer Research, Montreal Cancer Institute/CRCHUM, Centre de Hospitalier de Université de Montréal, Montréal, QC, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Saad
authors.affiliation: Quintiles, Hoofddorp, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Ivanescu
authors.affiliation: Astellas Pharma, Leiden, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Phung
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Medivation, San Francisco, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Abhyankar
authors.affiliation: OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Beer
authors.affiliation: Cliniques universitaires Saint-Luc, Bruxelles, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Astellas Medical Affairs, Global HEOR, Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Holmstrom
mesh_terms: D000368:Aged; D001842:Bone and Bones / Q000473:pathology*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D015897:Comorbidity; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications* / Q000453:epidemiology* / Q000473:pathology / Q000628:therapy; D011788:Quality of Life; D057566:Self Report