title: Enzalutamide in metastatic prostate cancer before chemotherapy.
abstract: BACKGROUND
  Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy.
  
  
  METHODS
  In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival.
  
  
  RESULTS
  The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment.
  
  
  CONCLUSIONS
  Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
authors.forename: Yohann
authors.initials: Y
authors.lastname: Loriot
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.forename: Suman
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.forename: Simon
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Evans
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
authors.forename: Choung-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Go
authors.initials: G
authors.lastname: Kimura
authors.forename: Paul
authors.initials: P
authors.lastname: Mainwaring
authors.forename: Harry
authors.initials: H
authors.lastname: Mansbach
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Noonberg
authors.forename: Frank
authors.initials: F
authors.lastname: Perabo
authors.forename: De
authors.initials: D
authors.lastname: Phung
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Taplin
authors.forename: Peter M
authors.initials: PM
authors.lastname: Venner
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000284:Administration, Oral; D059002:Androgen Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011859:Radiography; D011944:Receptors, Androgen; D016019:Survival Analysis
chemical_list: D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D010669:Phenylthiohydantoin; C540278:enzalutamide