title: Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel.
abstract: BACKGROUND
  Enzalutamide and abiraterone are new androgen-axis disrupting treatments for metastatic castration-resistant prostate cancer (mCRPC). We examined the response and outcomes of enzalutamide-treated mCRPC patients in the real-world context of prior treatments of abiraterone and/or docetaxel.
  
  
  METHODS
  We conducted a seven-institution retrospective study of mCRPC patients treated with enzalutamide between January 2009 and February 2014. We compared the baseline characteristics, PSA declines, PSA progression-free survival (PSA-PFS), duration on enzalutamide and overall survival (OS) across subgroups defined by prior abiraterone and/or docetaxel.
  
  
  RESULTS
  Of 310 patients who received enzalutamide, 36 (12%) received neither prior abiraterone nor prior docetaxel, 79 (25%) received prior abiraterone, 30 (10%) received prior docetaxel and 165 (53%) received both prior abiraterone and prior docetaxel. Within these groups, respectively, ⩾30% PSA decline was achieved among 67, 28, 43 and 24% of patients; PSA-PFS was 5.5 (95% CI 4.2-9.1), 4.0 (3.2-4.8), 4.1 (2.9-5.4) and 2.8 (2.5-3.2) months; median duration of enzalutamide was 9.1 (7.3-not reached), 4.7 (3.7-7.7), 5.4 (3.8-8.4) and 3.9 (3.0-4.6) months. Median OS was reached only for the patients who received both prior abiraterone and docetaxel and was 12.2 months (95% CI 10.7-16.5). 12-month OS was 78% (59-100%), 64% (45-90%), 77% (61-97%) and 51% (41-62%). Of 70 patients who failed to achieve any PSA decline on prior abiraterone, 19 (27%) achieved ⩾30% PSA decline with subsequent enzalutamide.
  
  
  CONCLUSIONS
  The activity of enzalutamide is blunted after abiraterone, after docetaxel, and still more after both, suggesting subsets of overlapping and distinct mechanisms of resistance.
authors.affiliation: 1] University of Washington, Seattle, WA, USA [2] Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Cheng
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gulati
authors.affiliation: British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Azad
authors.affiliation: Sidney Kimmel Cancer Center/Johns Hopkins University, Baltimore, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Nadal
authors.affiliation: City of Hope Cancer Center, Duarte, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Twardowski
authors.affiliation: Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA.
authors.forename: U N
authors.initials: UN
authors.lastname: Vaishampayan
authors.affiliation: Huntsman Cancer Institute/University of Utah, Salt Lake City, UT, USA.
authors.forename: N
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA.
authors.forename: E I
authors.initials: EI
authors.lastname: Heath
authors.affiliation: City of Hope Cancer Center, Duarte, CA, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: Sidney Kimmel Cancer Center/Johns Hopkins University, Baltimore, MA, USA.
authors.forename: H-T
authors.initials: HT
authors.lastname: Rehman
authors.affiliation: Tisch Cancer Institute/Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Leiter
authors.affiliation: Huntsman Cancer Institute/University of Utah, Salt Lake City, UT, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Batten
authors.affiliation: 1] University of Washington, Seattle, WA, USA [2] Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Montgomery
authors.affiliation: Tisch Cancer Institute/Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Galsky
authors.affiliation: Sidney Kimmel Cancer Center/Johns Hopkins University, Baltimore, MA, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Antonarakis
authors.affiliation: British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: K N
authors.initials: KN
authors.lastname: Chi
authors.affiliation: 1] University of Washington, Seattle, WA, USA [2] Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: E Y
authors.initials: EY
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001549:Benzamides; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; C089740:abiraterone