title: Enzalutamide in European and North American men participating in the AFFIRM trial.
abstract: OBJECTIVE
  To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311).
  
  
  METHODS
  Phase III, double-blind, placebo-controlled, multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis.
  
  
  RESULTS
  Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry.
  
  
  CONCLUSIONS
  This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions.
authors.affiliation: Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hirmand
authors.forename: Billy
authors.initials: B
authors.lastname: Franks
authors.forename: Gabriel P
authors.initials: GP
authors.lastname: Haas
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D004311:Double-Blind Method; D005060:Europe; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009570:Nitriles; D009656:North America; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: androgen receptor inhibitor; enzalutamide; metastatic castration-resistant prostate cancer