title: Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients.
abstract: BACKGROUND
  The activity of enzalutamide after prior treatment with both abiraterone acetate (abiraterone) and docetaxel has been examined in several retrospective studies. However, limited data are available on the efficacy of enzalutamide following abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC).
  
  
  OBJECTIVE
  To compare the activity of enzalutamide after abiraterone in docetaxel-experienced and docetaxel-naive mCRPC patients.
  
  
  METHODS
  The British Columbia Cancer Agency Cancer Registry was searched for mCRPC patients who received enzalutamide after prior abiraterone. Clinicopathologic characteristics, confirmed prostate-specific antigen (PSA) response rates (PSA decline ≥ 50% confirmed ≥ 3 wk later), and survival data were collected.
  
  
  METHODS
  Outcomes on enzalutamide were compared between docetaxel-experienced and docetaxel-naive patients using chi-square for PSA response and log-rank test for time to PSA progression and overall survival (OS). Univariate analysis was performed to identify variables associated with confirmed PSA response on enzalutamide, using either chi-square for categorical variables or logistic regression for continuous variables.
  
  
  CONCLUSIONS
  A total of 115 patients received enzalutamide after abiraterone: 68 had received prior docetaxel and 47 were docetaxel naive. Median time on enzalutamide was 4.1 mo. Confirmed PSA response rates (22% vs 26%; p=0.8), median time to radiologic/clinical progression (4.6 mo vs 6.6 mo; p=0.6), and median OS (10.6 mo vs 8.6 mo; p=0.2) did not differ significantly between docetaxel-experienced and docetaxel-naive patients. No clinical variables (including prior response to abiraterone) were found to associate significantly with confirmed PSA response to enzalutamide.
  
  
  CONCLUSIONS
  Antitumour activity of enzalutamide following abiraterone was limited in mCRPC patients irrespective of prior docetaxel use. Identifying clinical and molecular factors predictive of response to enzalutamide remains a high priority for future research.
  
  
  RESULTS
  We looked at the effectiveness of enzalutamide after abiraterone acetate for treatment of advanced prostate cancer. We found that patients who had received docetaxel chemotherapy before abiraterone gained similar benefit from enzalutamide compared with patients who had not received docetaxel. These results suggest that earlier treatment with docetaxel does not have a large impact on the activity of enzalutamide after abiraterone.
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.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Eigl
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: R Nevin
authors.initials: RN
authors.lastname: Murray
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. Electronic address: kchi@bccancer.bc.ca.
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
mesh_terms: D000069501:Abiraterone Acetate; D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D000077143:Docetaxel; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D000736:Androstenes; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate
keywords: Abiraterone; Abiraterone acetate; Castration-resistant prostate cancer; Docetaxel; Enzalutamide