title: Enzalutamide in Patients With Castration-Resistant Prostate Cancer Progressing After Docetaxel: Retrospective Analysis of the Swiss Enzalutamide Named Patient Program.
abstract: Enzalutamide is a second-generation androgen receptor (AR) inhibitor that binds to and blocks the AR with higher affinity than previously available AR inhibitors. High activity has been proven in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and in chemotherapy-naive patients with mCRPC. However, its activity in patients previously treated with other novel agents (for example, abiraterone and/or cabazitaxel), remains controversial.
  
  
  
  The aim of this retrospective analysis of the Swiss Enzalutamide Named Patient Program was to evaluate clinical efficacy and safety of enzalutamide treatment in patients with mCRPC progressing after docetaxel and other lines of therapy considering different treatment sequences. We report on 44 patients treated with enzalutamide.
  
  
  
  The median survival time from diagnosis of CPRC was 41.1 months (95% confidence interval [CI], 32.3-49.8 months). Enzalutamide was used as a second, third, fourth, fifth, sixth, or seventh-line therapy in 13%, 20%, 31%, 20%, 11%, and 2% of patients. The median duration of enzalutamide treatment was 3.0 months (range, 1-21 months). Median progression-free survival was 3.0 months (95% CI, 2.4-3.7 months). The estimated median overall survival was 6.3 months (95% CI, 4.6-8.1 months). Sixteen patients (36.4%) had a prostate-specific antigen decrease of ≥ 30%, and 11 patients (25.0%) of ≥ 50%, respectively. In multivariate analysis, the absence of previous therapy with abiraterone and a prostate-specific antigen response of ≥ 50% on enzalutamide therapy were significantly associated with overall survival on enzalutamide treatment.
  
  
  
  Our results show that enzalutamide has modest activity in extensively pretreated patients. However, there is a subgroup of patients achieving benefit from enzalutamide therapy even after pretreatment with abiraterone.
authors.affiliation: Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Papazoglou
authors.affiliation: Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Luciano
authors.initials: L
authors.lastname: Wannesson
authors.affiliation: Department of Medical Oncology, University Hospital Lausanne, CHUV, Lausanne, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Berthold
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Chur, Chur, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Cathomas
authors.affiliation: Department of Medical Oncology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors.forename: Silke
authors.initials: S
authors.lastname: Gillessen
authors.affiliation: Department of Medical Oncology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Rothermundt
authors.affiliation: Medical Oncology Practice, Biel, Switzerland.
authors.forename: Loretta
authors.initials: L
authors.lastname: Hasler
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Luzern, Luzern, Switzerland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Winterhalder
authors.affiliation: Department of Medical Oncology, Bürgerspital Solothurn, Solothurn, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Barth
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Olten, Olten, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Mingrone
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Olten, Olten, Switzerland.
authors.forename: Catrina Uhlmann
authors.initials: CU
authors.lastname: Nussbaum
authors.affiliation: Medical Oncology Practice, Biel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: von Rohr
authors.affiliation: Department of Medical Oncology, Cantonal Hospital Aarau, Aarau, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: von Burg
authors.affiliation: Department of Medical Oncology, Triemlispital Zürich, Zürich, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Schmid
authors.affiliation: Onkologie Länggasse, Bern, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Richner
authors.affiliation: Medical Oncology Practice, Winterthur, Switzerland.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Baumann
authors.affiliation: Department of Medical Oncology, Waidspital Zürich, Zürich, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Kühne
authors.affiliation: Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Stenner
authors.affiliation: Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. Electronic address: sacha.rothschild@usb.ch.
authors.forename: Sacha I
authors.initials: SI
authors.lastname: Rothschild
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001549:Benzamides; D000077143:Docetaxel; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: Abiraterone; Androgen receptor antagonist; Antihormonal drugs; PSA; Treatment sequence