title: A retrospective, Canadian multi-center study examining the impact of prior response to abiraterone acetate on efficacy of docetaxel in metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  Questions about optimal sequencing of systemic therapy in metastatic castration-resistant prostate cancer (mCRPC) and whether cross-resistance occurs between different drugs remain largely unanswered. Previous studies have produced conflicting data on the activity of docetaxel in patients who did not attain a prostate-specific antigen (PSA) response to abiraterone acetate (abiraterone). We investigated whether the biochemical response to abiraterone is associated with efficacy of subsequent docetaxel therapy.
  
  
  METHODS
  mCRPC patients treated with docetaxel after abiraterone were retrospectively identified at three Canadian institutions. Patients who had also received docetaxel prior to abiraterone were termed "docetaxel-experienced," while those not treated with docetaxel prior to abiraterone were termed "docetaxel-naïve." Treatment outcomes on docetaxel were stratified by prior response to abiraterone and compared using χ(2) -square test for confirmed PSA response rate (≥ 50% decline from baseline maintained for ≥ 3 weeks) and the log-rank method for progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Eighty-six patients were treated with abiraterone, of whom 49 were docetaxel-experienced and 37 were docetaxel-naïve. Prior PSA response to abiraterone was no decline, <50% decline and ≥ 50% decline in 37%, 26%, and 37% of patients respectively. The overall PSA response rate to docetaxel was 34.9%, median PFS was 4.0 months and median OS was 11.66 months. Notably, no differences were seen in confirmed PSA response rates (38% vs. 36% vs. 31%, P = 0.86), median PFS (4.04 months vs. 3.94 months vs. 4.24 months, P = 0.43) and median OS (11.86 months vs. 15.38 months vs. 11.00 months, P = 0.56) on docetaxel for patients with no PSA decline, <50% decline and ≥ 50% decline on abiraterone respectively. Importantly, PSA response rates to docetaxel were comparable in the docetaxel-experienced and docetaxel-naïve cohorts and were not linked to prior response to abiraterone in either group.
  
  
  CONCLUSIONS
  Activity of docetaxel was not associated with the biochemical response to prior abiraterone therapy. These data suggest that prior response to abiraterone should not influence decisions on subsequent use of docetaxel in mCRPC.
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Arun A
authors.initials: AA
authors.lastname: Azad
authors.forename: Raya
authors.initials: R
authors.lastname: Leibowitz-Amit
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Eigl
authors.forename: Renee
authors.initials: R
authors.lastname: Lester
authors.forename: J Connor
authors.initials: JC
authors.lastname: Wells
authors.forename: R Nevin
authors.initials: RN
authors.lastname: Murray
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002170:Canada; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: abiraterone; abiraterone acetate; castration-resistant prostate cancer; docetaxel; prostate cancer