title: Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of study COU-AA-302.
abstract: BACKGROUND
  Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy.
  
  
  OBJECTIVE
  Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients.
  
  
  METHODS
  This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial.
  
  
  METHODS
  Patients were grouped by concomitant BTT use or no BTT use.
  
  
  METHODS
  Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models.
  
  
  CONCLUSIONS
  While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG deterioration (HR 0.75; p<0.001) and time to opiate use for cancer-related pain (HR 0.80; p=0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients.
  
  
  CONCLUSIONS
  AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT.
  
  
  RESULTS
  Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00887198.
authors.affiliation: University of Montréal, Montréal, Québec, Canada. Electronic address: fredsaad@videotron.ca.
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.affiliation: Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Shore
authors.affiliation: University Hospital Leuven, Leuven, Belgium.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
authors.affiliation: Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.affiliation: University of Western Sydney School of Medicine, Ingham Institute, Liverpool, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: de Souza
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.affiliation: Hematology and Oncology Clinics of Australia, Brisbane, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Mainwaring
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.affiliation: Oregon Health & Science University Knight Cancer Institute, Portland, OR, USA.
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.affiliation: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.affiliation: Laval University, Québec City, Québec, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Griffin
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: De Porre
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Londhe
authors.affiliation: Janssen Research & Development, San Diego, CA, USA.
authors.forename: Thian
authors.initials: T
authors.lastname: Kheoh
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.affiliation: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Janssen Research & Development, Menlo Park, CA, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Molina
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
mesh_terms: D000069501:Abiraterone Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016017:Odds Ratio; D011241:Prednisone / Q000627:therapeutic use; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D065088:Steroid Synthesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D065088:Steroid Synthesis Inhibitors; D000069501:Abiraterone Acetate; D011241:Prednisone
keywords: Abiraterone acetate; Bone-targeted therapy; Chemotherapy-naïve; Metastatic castration-resistant prostate cancer