title: Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study.
abstract: Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28-0.37; p<0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67-0.88; p=0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9-22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1-5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2-not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8-34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991.
  
  
  
  According to data from longer follow-up, enzalutamide continued to provide benefit over placebo in patients with metastatic castration-resistant prostate cancer.
authors.affiliation: Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA. Electronic address: beert@ohsu.edu.
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.affiliation: Duke Cancer Institute, Durham, NC, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Rathkopf
authors.affiliation: Institut Gustave-Roussy, Villejuif, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: San Camillo and Forlanini Hospitals, Rome, Italy.
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.affiliation: University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA.
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.affiliation: Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.affiliation: UC Davis Cancer Center, Sacramento, CA, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Evans
authors.affiliation: Asan Medical Center, Seoul, Korea.
authors.forename: Choung-Soo
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Nippon Medical School, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kimura
authors.affiliation: Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.affiliation: University of Montreal Hospital Center, Montreal, QC, Canada.
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.affiliation: Skåne University Hospital, Malmö, Sweden.
authors.forename: Anders S
authors.initials: AS
authors.lastname: Bjartell
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Borre
authors.affiliation: Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Mulders
authors.affiliation: Tampere University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Teuvo L
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Medivation, San Francisco, CA, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Parli
authors.affiliation: Medivation, San Francisco, CA, USA.
authors.forename: Suha
authors.initials: S
authors.lastname: Sari
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: Steve
authors.initials: S
authors.lastname: van Os
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: Ad
authors.initials: A
authors.lastname: Theeuwes
authors.affiliation: Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: Androgen receptor signaling inhibitor; Enzalutamide; Metastatic castration-resistant prostate cancer; Overall survival; Radiographic progression-free survival