title: Efficacy outcomes by baseline prostate-specific antigen quartile in the AFFIRM trial.
abstract: BACKGROUND
  Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer (PCa) after docetaxel in the randomised, phase 3, double-blind, placebo-controlled, multinational Patients with Progressive Castration-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy (AFFIRM) trial (NCT00974311). Prostate-specific antigen (PSA) is commonly used as a marker of PCa disease burden, and the relationship of baseline PSA level to consequent treatment effect is of clinical interest.
  
  
  OBJECTIVE
  Exploratory analysis to evaluate any differences in patient characteristics and efficacy outcomes by baseline PSA level in the AFFIRM trial.
  
  
  METHODS
  Post hoc subanalysis of all randomised patients (n=1199) from the AFFIRM trial.
  
  
  METHODS
  Participants were randomly assigned in a two-to-one ratio to receive oral enzalutamide 160 mg/d or placebo.
  
  
  METHODS
  The major clinical efficacy end points were overall survival (OS), radiographic progression-free survival (rPFS), and time to PSA progression (TTPP) versus placebo; baseline characteristics, treatment duration, and subsequent antineoplastic therapy were compared by baseline PSA quartile.
  
  
  CONCLUSIONS
  Baseline PSA quartiles corresponded to the following PSA groups: <40 ng/ml (n=299), 40 to <111 ng/ml (n=300), 111 to <406 ng/ml (n=300), and ≥406 ng/ml (n=300). Enzalutamide consistently improved OS, rPFS, and TTPP compared with placebo across all subgroups, regardless of baseline PSA level. Hazard ratios for improvements in OS were 0.55 (95% confidence interval [CI], 0.36-0.85), 0.69 (95% CI, 0.47-1.02), 0.73 (95% CI, 0.53-1.01), and 0.53 (95% CI, 0.39-0.73) for PSA groups 1-4, respectively. The post hoc design of this analysis was not statistically powered to assess the relationship between baseline PSA and clinical efficacy outcomes.
  
  
  CONCLUSIONS
  This post hoc analysis of the AFFIRM trial demonstrates consistent benefits in OS, rPFS, and TTPP with enzalutamide regardless of baseline disease severity, as assessed by PSA.
  
  
  RESULTS
  Exploratory post hoc analysis of the AFFIRM trial showed that enzalutamide improves overall survival, radiographic progression-free survival, and time to prostate-specific antigen progression compared with placebo regardless of baseline disease severity, as assessed by prostate-specific antigen.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00974311.
authors.affiliation: University of Montreal Hospital Centre, Montreal, QC, Canada. Electronic address: fred.saad@umontreal.ca.
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.affiliation: Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
authors.affiliation: Carolina Urologic Research Center, Myrtle Beach, SC, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Shore
authors.affiliation: Gustave Roussy, Cancer Campus Grand Paris, University of Paris Sud, Villejuif, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Gustave Roussy, Cancer Campus Grand Paris, University of Paris Sud, Villejuif, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Medivation, Inc., San Francisco, CA, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hirmand
authors.affiliation: Astellas Global Medical Affairs, Inc., Northbrook, IL, USA.
authors.forename: Billy
authors.initials: B
authors.lastname: Franks
authors.affiliation: Astellas Global Medical Affairs, Inc., Northbrook, IL, USA.
authors.forename: Gabriel P
authors.initials: GP
authors.lastname: Haas
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001315:Australia; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005060:Europe; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D009656:North America; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D013019:South Africa; D013020:South America; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: AFFIRM trial; Androgen receptor inhibitor; Enzalutamide; Metastatic castration-resistant prostate cancer; Prostate-specific antigen