title: Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results.
abstract: BACKGROUND
  Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability.
  
  
  OBJECTIVE
  To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr.
  
  
  METHODS
  Open-label, single-arm study in patients with HNPC and noncastrate testosterone (≥230 ng/dl).
  
  
  METHODS
  Oral enzalutamide 160mg/d until disease progression or unacceptable toxicity.
  PSA response (≥80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk).
  
  
  CONCLUSIONS
  The median (range) age was 73 (48-86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92-100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk.
  
  
  CONCLUSIONS
  Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD.
  
  
  RESULTS
  In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naïve prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density.
  
  
  BACKGROUND
  NCT01302041.
authors: Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium. Electronic address: bertrand.tombal@uclouvain.be.
authors: Bertrand
authors: B
authors: Tombal
authors: Aarhus University Hospital, Aarhus, Denmark.
authors: Michael
authors: M
authors: Borre
authors: Herlev Hospital, Herlev, Denmark.
authors: Per
authors: P
authors: Rathenborg
authors: AZ Groeninge Kortrijk, Kortrijk, Belgium.
authors: Patrick
authors: P
authors: Werbrouck
authors: UZ Leuven, Leuven, Belgium.
authors: Hendrik
authors: H
authors: Van Poppel
authors: Klinik und Poliklinik für Urologie, RWTH University Aachen, Aachen, Germany.
authors: Axel
authors: A
authors: Heidenreich
authors: Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Peter
authors: P
authors: Iversen
authors: UZ Brussel, Brussels, Belgium.
authors: Johan
authors: J
authors: Braeckman
authors: Univerzita Karlova v Praze, Prague, Czech Republic.
authors: Jiri
authors: J
authors: Heracek
authors: Astellas Pharma Global Development, Leiden, The Netherlands.
authors: Edwina
authors: E
authors: Baskin-Bey
authors: Astellas Pharma Global Development, Leiden, The Netherlands.
authors: Taoufik
authors: T
authors: Ouatas
authors: Astellas Pharma Global Development, Northbrook, IL, USA.
authors: Frank
authors: F
authors: Perabo
authors: Astellas Pharma Global Development, Leiden, The Netherlands.
authors: De
authors: D
authors: Phung
authors: Astellas Pharma Global Development, Leiden, The Netherlands.
authors: Benoit
authors: B
authors: Baron
authors: Medivation Inc., San Francisco, CA, USA.
authors: Mohammad
authors: M
authors: Hirmand
authors: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors: Matthew R
authors: MR
authors: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001549:Benzamides; D017024:Chemotherapy, Adjuvant; D005500:Follow-Up Studies; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Androgen receptor; Enzalutamide; Hormone-naïve prostate cancer; Prostate-specific antigen response