title: Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis.
abstract: BACKGROUND
  The degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial.
  
  
  OBJECTIVE
  To examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone.
  
  
  METHODS
  Metastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide.
  
  
  METHODS
  The primary end point was overall survival (OS). Secondary end points were association between OS and posttreatment prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed.
  
  
  CONCLUSIONS
  We identified 137 patients who prior to enzalutamide had progressed following a median of eight cycles of docetaxel and seven courses of abiraterone. The median time on enzalutamide was 3.2 mo; median OS from the time patients started enzalutamide was 8.3 mo (95% confidence interval, 6.8-9.8). Only 45 (38%) and 22 (18%) patients had PSA declines (unconfirmed) >30% and 50%, respectively. Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p=0.001 and 12.6 vs 7.4 mo; p=0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS.
  
  
  CONCLUSIONS
  Median OS on enzalutamide following disease progression on taxane-based chemotherapy and abiraterone was modest, but patients who experience a PSA decline >30% or 50%, respectively, with enzalutamide in this setting had longer survival.
  
  
  RESULTS
  Enzalutamide produces modest prostate-specific antigen (PSA) responses in patients progressing following chemotherapy and abiraterone. Despite a modest PSA response, survival may still be improved.
authors.affiliation: Copenhagen Prostate Cancer Centre, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark. Electronic address: klausbrasso@hotmail.com.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brasso
authors.affiliation: Copenhagen Prostate Cancer Centre, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Frederik B
authors.initials: FB
authors.lastname: Thomsen
authors.affiliation: Department of Urology, Ulm University Medical Centre, Ulm, Germany.
authors.forename: Andres J
authors.initials: AJ
authors.lastname: Schrader
authors.affiliation: Urologische Klinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Sebastian C
authors.initials: SC
authors.lastname: Schmid
authors.affiliation: Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Lorente
authors.affiliation: Urologische Klinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.affiliation: Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.affiliation: Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: von Klot
authors.affiliation: Department of Urology, Muenster University Medical Centre, Muenster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Boegemann
authors.affiliation: Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000736:Androstenes / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D057176:Compassionate Use Trials; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D057915:Drug Substitution; D005060:Europe; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000736:Androstenes; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: Abiraterone; Castration-resistant prostate cancer; Docetaxel; Enzalutamide; PSA; Survival