title: The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer.
abstract: Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer.
  
  
  
  To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease.
  
  
  
  One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup analyses included nonvisceral (only bone and/or nodal; n=1513), visceral (lung and/or liver; n=204), low-volume bone disease (<4 bone metastases; n=867), high-volume bone disease (≥4 bone metastases; n=850), lymph node only disease (n=195).
  
  
  
  Oral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy.
  
  
  
  Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc.
  
  
  
  Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low- or high-volume bone disease (HR, 0.16; 95% CI, 0.11-0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (<1) across all disease subgroups, although 95% CI was >1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease.
  
  
  
  Enzalutamide provided clinically significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease.
  
  
  
  Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease or widespread bone disease-benefitted from enzalutamide, an active well-tolerated therapy.
authors.affiliation: Department of Urology, UC Davis Comprehensive Cancer Center, Sacramento, CA, USA. Electronic address: cpevans@ucdavis.edu.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Evans
authors.affiliation: Medical Oncology Division, University of Washington/Seattle Cancer Care Alliance, Seattle, WA, USA.
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.affiliation: Department of Urology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Keane
authors.affiliation: Division of Urologic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Andriole
authors.affiliation: Department of Surgery, University of Montreal Health Center, Montreal, Canada.
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.affiliation: Copenhagen Prostate Cancer Center, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.affiliation: Department of Urology, Asan Medical Center, Seoul, South Korea.
authors.forename: Choung-Soo
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Urology, Nippon Medical School Hospital, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kimura
authors.affiliation: Division of Medical Oncology and Urology, Duke Cancer Institute, Durham, NC, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.affiliation: Department of Cancer Medicine, Institut Gustave-Roussy, Villejuif, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Drug Development Unit, Institute of Cancer Research, Royal Marsden Hospital, London, UK.
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
authors.affiliation: Department of Early Clinical Development, Medivation, Inc., San Francisco, CA, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Noonberg
authors.affiliation: Department of Medical Affairs, Medivation, Inc., San Francisco, CA, USA.
authors.forename: Hank
authors.initials: H
authors.lastname: Mansbach
authors.affiliation: Department of Biostatistics, Medivation, Inc., San Francisco, CA, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Astellas Pharma, Inc., Northbrook, IL, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Perabo
authors.affiliation: Department of Hematology and Medical Oncology, OHSU Knight Cancer Institute, Portland, OR, USA.
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.affiliation: Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
mesh_terms: D000368:Aged; D059002:Androgen Receptor Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology*; D015996:Survival Rate; D047368:Tumor Burden
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: Androgen receptor; Castration-resistant prostatic cancer; Enzalutamide