title: Comparative Assessment of Efficacies Between 2 Alternative Therapeutic Sequences With Novel Androgen Receptor-Axis-Targeted Agents in Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.
abstract: The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents in patients with docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC).
  
  
  
  This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively.
  
  
  
  Of these patients, 49 and 59 received ARAT therapy with the AA-to-Enz sequence (AA-to-Enz group) and with the reverse sequence (Enz-to-AA group), respectively. No significant differences in the baseline characteristics were noted between the 2 groups. In the overall patient population, the PSA response rate to the second-line ARAT agent (21.3%) was significantly lower than that of the first-line ARAT agent (58.3%). The combined PSA PFS in the AA-to-Enz group (median, 18.4 months) was significantly superior to that of the Enz-to-AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (ie, AA-to-Enz vs. Enz-to-AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients. However, there was no significant difference in overall survival (OS) between the 2 groups.
  
  
  
  Although cross-resistance between ARAT agents is a common phenomenon in docetaxel-naïve patients with mCRPC, different efficacies were observed favoring the AA-to-Enz rather than Enz-to-AA sequence in this series with respect to combined PSA PFS but not OS.
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: hideakimiyake@hotmail.com.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takuto
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furuse
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000069501:Abiraterone Acetate / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D007610:Kallikreins; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017430:Prostate-Specific Antigen; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D010669:Phenylthiohydantoin; C540278:enzalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate
keywords: Abiraterone acetate; Cross-resistance; Enzalutamide; Sequential therapy