title: Abiraterone in metastatic prostate cancer without previous chemotherapy.
abstract: BACKGROUND
  Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy.
  
  
  METHODS
  In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival.
  
  
  RESULTS
  The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone-prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P=0.01) but did not cross the efficacy boundary. Abiraterone-prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone.
  
  
  CONCLUSIONS
  Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.).
authors.affiliation: Genitourinary Medical Oncology Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA. ryanc@medicine.ucsf.edu
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.forename: Arturo
authors.initials: A
authors.lastname: Molina
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.forename: Paul
authors.initials: P
authors.lastname: de Souza
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.forename: Paul
authors.initials: P
authors.lastname: Mainwaring
authors.forename: Josep M
authors.initials: JM
authors.lastname: Piulats
authors.forename: Siobhan
authors.initials: S
authors.lastname: Ng
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.forename: Ethan
authors.initials: E
authors.lastname: Basch
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Dirk
authors.initials: D
authors.lastname: Schrijvers
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.forename: Som D
authors.initials: SD
authors.lastname: Mukherjee
authors.forename: Henrik
authors.initials: H
authors.lastname: Suttmann
authors.forename: Winald R
authors.initials: WR
authors.lastname: Gerritsen
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Flaig
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Yu
authors.forename: Eleni
authors.initials: E
authors.lastname: Efstathiou
authors.forename: Allan
authors.initials: A
authors.lastname: Pantuck
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Taplin
authors.forename: Youn
authors.initials: Y
authors.lastname: Park
authors.forename: Thian
authors.initials: T
authors.lastname: Kheoh
authors.forename: Thomas
authors.initials: T
authors.lastname: Griffin
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
mesh_terms: D000069501:Abiraterone Acetate; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016019:Survival Analysis
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D000069501:Abiraterone Acetate; D011241:Prednisone