title: The Effect of Time to Castration Resistance on Outcomes With Abiraterone and Enzalutamide in Metastatic Prostate Cancer.
abstract: Abiraterone and enzalutamide are 2 novel androgen receptor (AR)-targeting therapies that improve survival in patients with metastatic castration-resistant prostate cancer. The factors that predict abiraterone and enzalutamide response are lacking. The objective of the present study was to determine whether the outcomes from primary androgen deprivation therapy (ADT) could predict the outcomes with subsequent novel AR-targeting therapies.
  
  
  
  We identified 80 consecutive patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide. Cox regression models were used to analyze the relationships between the primary ADT response and the primary outcome of progression-free survival (PFS) after initiating novel hormonal therapy. The secondary outcomes included prostate-specific antigen decline and overall survival. The survival probabilities were plotted using the Kaplan-Meier method, and the differences assessed with the log-rank test.
  
  
  
  The time to castration resistance with primary ADT showed a significant association with both PFS and overall survival after initiating novel hormone therapy (P = .032 and P = .028, respectively). Patients with progression during primary ADT before 1 year had a median PFS of 3.4 months compared with a median PFS of 7.6 and 8.1 months for patients whose time to castration resistance was ≥ 1 and ≤ 5 years (P = .008) and > 5 years (P = .026), respectively. However, the time to castration resistance was not an independent predictor of survival or the PSA response with novel AR-targeting therapy on multivariate analysis.
  
  
  
  A rapid time to progression during primary ADT was associated with poor outcomes but was not an independent predictor of the response to enzalutamide or abiraterone.
authors.affiliation: Department of Urology, Oakland University William Beaumont School of Medicine, Rochester, MI.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hung
authors.affiliation: Department of Public Health Sciences, Josephine Ford Cancer Institute, Henry Ford Health System, Detroit, MI.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Taylor
authors.affiliation: Department of Public Health Sciences, Josephine Ford Cancer Institute, Henry Ford Health System, Detroit, MI.
authors.forename: George W
authors.initials: GW
authors.lastname: Divine
authors.affiliation: Department of Urology, Oakland University William Beaumont School of Medicine, Rochester, MI.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hafron
authors.affiliation: Department of Hematology/Oncology, Josephine Ford Cancer Institute, Henry Ford Health System, Detroit, MI. Electronic address: chwang2@hfhs.org.
authors.forename: Clara
authors.initials: C
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000736:Androstenes / Q000008:administration & dosage* / Q000627:therapeutic use; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D012044:Regression Analysis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000736:Androstenes; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: Androgen deprivation; Androgen receptor signaling inhibitor; Hormonal therapy; Novel AR-targeted therapy; Predictive marker