title: Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation.
abstract: BACKGROUND
  Abiraterone Acetate (AA) and Enzalutamide (Enz) are effective hormonal treatments in mCRPC patients. Retrospective studies suggested clinical cross-resistance between Enz and AA. However, 12.8-39.1% of patients previously treated with docetaxel (Doc) and AA do respond to Enz. These responders have not been characterized.
  
  
  METHODS
  102 Enz treated mCRPC patients after AA and Doc treatment were included in this study. Differences in patient characteristics and previous treatment outcomes between PSA responders and non-responders on Enz were evaluated.
  
  
  RESULTS
  Median Progression-Free Survival was 12.2 weeks (95%CI 11.7-14.3) and Overall Survival 43.5 weeks (95%CI 37.4-61.2). There were 26 (25%) Enz-responders and 76 (75%) non-responders. Significant higher percentages of Gleason scores ≥ 8 and PSA doubling times (PSA-DT) <3 months were found in Enz responders than in non-responders. The interval between end of AA and start of Enz treatment (IAE) for responders was 24.6 weeks (IQR 4.0-48.1) and 8.9 weeks for non-responders (IQR 3.7-25.9) (P = 0.08). In an IAE <40 days subgroup (34 patients), Enz responses were related to AA non-responsiveness, while univariate and logistic regression analysis of baseline criteria of a subgroup of patients with an IAE ≥ 40 (68 patients) revealed significant differences in baseline PSA levels, PSA-DT <3 months, Gleason scores ≥ 8 and IAE's between Enz responders and non-responders.
  
  
  CONCLUSIONS
  PSA response to Enz after previous AA and Doc treatment was associated with a longer IAE, a higher Gleason score and a PSA-DT <3 months. Identification of these patients might be of value for sequencing of treatment options.
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Badrising
authors.affiliation: Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: van der Noort
authors.affiliation: Department of Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.affiliation: Department of Oncology & Prostate Cancer Center, Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hamberg
authors.affiliation: Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Inge M
authors.initials: IM
authors.lastname: van Oort
authors.affiliation: Department of Oncology Tergooi Ziekenhuizen, Blaricum, the Netherlands.
authors.forename: Hendrik P
authors.initials: HP
authors.lastname: van den Berg
authors.affiliation: Department of Oncology, Sint Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Maartje
authors.initials: M
authors.lastname: Los
authors.affiliation: Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Maureen J B
authors.initials: MJ
authors.lastname: Aarts
authors.affiliation: Department of Oncology, Isala Klinieken, Zwolle, the Netherlands.
authors.forename: Jules L L M
authors.initials: JL
authors.lastname: Coenen
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Department of Urology, University of Groningen, Groningen, the Netherlands.
authors.forename: Igle J
authors.initials: IJ
authors.lastname: de Jong
authors.affiliation: Department of Oncology, OLVG Hospital, Amsterdam, the Netherlands.
authors.forename: Emile D
authors.initials: ED
authors.lastname: Kerver
authors.affiliation: Department of Internal Medicine, Medisch Centrum Alkmaar, Alkmaar, the Netherlands.
authors.forename: Suzan
authors.initials: S
authors.lastname: Vrijaldenhoven
authors.affiliation: Department of Oncology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: van Voorthuizen
authors.affiliation: Department of Internal Medicine/Oncology, Atrium-Orbis Medical Center, Heerlen, the Netherlands.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Warmerdam
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: John B
authors.initials: JB
authors.lastname: Haanen
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Andries M
authors.initials: AM
authors.lastname: Bergman
mesh_terms: D000368:Aged; D000736:Androstenes / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001549:Benzamides; D018572:Disease-Free Survival; D000077143:Docetaxel; D016903:Drug Monitoring; D019008:Drug Resistance, Neoplasm; D057915:Drug Substitution / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: AR plasticity; abiraterone; cross-resistance; docetaxel; enzalutamide; prostate cancer