title: Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials.
abstract: BACKGROUND
  The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively.
  
  
  METHODS
  Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model.
  
  
  RESULTS
  Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups.
  
  
  CONCLUSIONS
  OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis.
  
  
  BACKGROUND
  COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France karim.fizazi@igr.fr.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Flaig
authors.affiliation: Saarland University, Homburg/Saar, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stöckle
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Rathkopf
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco.
authors.forename: C J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Janssen Research & Development, San Diego.
authors.forename: T
authors.initials: T
authors.lastname: Kheoh
authors.affiliation: Janssen Research & Development, Raritan.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Janssen Global Services, Raritan.
authors.forename: M B
authors.initials: MB
authors.lastname: Todd
authors.affiliation: Janssen Research & Development, Los Angeles.
authors.forename: T W
authors.initials: TW
authors.lastname: Griffin
authors.affiliation: Janssen Research & Development, Menlo Park, USA.
authors.forename: A
authors.initials: A
authors.lastname: Molina
authors.affiliation: Saarland University, Homburg/Saar, Germany.
authors.forename: C H
authors.initials: CH
authors.lastname: Ohlmann
mesh_terms: D000069501:Abiraterone Acetate / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000737:Androstenols / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011241:Prednisone / Q000008:administration & dosage; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000737:Androstenols; D000069501:Abiraterone Acetate; D011241:Prednisone
keywords: Gleason score; abiraterone acetate; chemotherapy-naïve; post-chemotherapy; prostate cancer