title: Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer: results from PREVAIL.
abstract: BACKGROUND
  Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial.
  
  
  METHODS
  PREVAIL was a randomised, double-blind, multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 845) in chemotherapy-naive men with metastatic castration-resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged <75 years was pre-specified for the coprimary end points and adverse events (AEs).
  
  
  RESULTS
  Among 609 elderly patients (35%) who participated in PREVAIL, median treatment duration was 16.6 and 5.0 months in the enzalutamide and placebo arms, respectively. In the elderly subgroup, OS was greater with enzalutamide than with placebo [32.4 months (95% confidence interval (CI) 27.7-not yet reached] versus 25.1 months (95% CI 22.6-28.0); hazard ratio (HR) = 0.61 (95% CI 0.47-0.79); P = 0.0001], as was rPFS [not yet reached (95% CI 12.3-not yet reached) versus 3.7 months (95% CI 3.6-5.3); HR = 0.17 (95% CI 0.12-0.24); P < 0.0001]. Irrespective of treatment assignment, incidence of AEs was similar between the two age groups, except for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)].
  
  
  CONCLUSIONS
  Elderly men benefited from treatment with enzalutamide in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged <75 years. Age and enzalutamide treatment were associated with a higher incidence of falls.
  
  
  BACKGROUND
  NCT01212991, ClinicalTrials.gov.
authors.affiliation: Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland Division of Oncology, Portland VA Medical Center, Portland, USA graffj@ohsu.edu.
authors.forename: J N
authors.initials: JN
authors.lastname: Graff
authors.affiliation: Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Baciarello
authors.affiliation: Divisions of Medical Oncology and Urology, Duke University Medical Center and the Duke Cancer Institute, Durham.
authors.forename: A J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Division of Medical Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Higano
authors.affiliation: Copenhagen Prostate Cancer Center, Rigshospitalet, University of Copenhagen, København, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Department of Medical Oncology, University of Colorado Cancer Center, Aurora.
authors.forename: T W
authors.initials: TW
authors.lastname: Flaig
authors.affiliation: Medivation, Inc., San Francisco, USA.
authors.forename: D
authors.initials: D
authors.lastname: Forer
authors.affiliation: Medivation, Inc., San Francisco, USA.
authors.forename: T
authors.initials: T
authors.lastname: Parli
authors.affiliation: Astellas Pharma Global Development, Inc., Leiden, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Phung
authors.affiliation: Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland.
authors.forename: T M
authors.initials: TM
authors.lastname: Beer
authors.affiliation: Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
authors.forename: C N
authors.initials: CN
authors.lastname: Sternberg
mesh_terms: D000058:Accidental Falls / Q000706:statistics & numerical data; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059002:Androgen Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010919:Placebos; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: PREVAIL trial; elderly patients; enzalutamide; metastatic castration-resistant prostate cancer