Long-Term Antitumor Activity and Safety of Enzalutamide Monotherapy in Hormone Naïve Prostate Cancer: 3-Year Open Label Followup Results

No AccessJournal of UrologyAdult Urology1 Feb 2018Long-Term Antitumor Activity and Safety of Enzalutamide Monotherapy in Hormone Naïve Prostate Cancer: 3-Year Open Label Followup Results Bertrand Tombal, Michael Borre, Per Rathenborg, Patrick Werbrouck, Hendrik Van Poppel, Axel Heidenreich, Peter Iversen, Johan Braeckman, Jiri Heracek, Benoit Baron, Andrew Krivoshik, Mohammad Hirmand, and Matthew R. Smith Bertrand TombalBertrand Tombal Cliniques universitaires Saint-Luc, Brussels, Belgium Financial interest and/or other relationship with Astellas Pharma, Inc., Pfizer, Inc. and Medivation, Inc. More articles by this author , Michael BorreMichael Borre Aarhus University Hospital, Aarhus, Denmark More articles by this author , Per RathenborgPer Rathenborg Herlev Hospital, Herlev, Denmark More articles by this author , Patrick WerbrouckPatrick Werbrouck AZ Groeninge Kortrijk, Kortrijk, Belgium More articles by this author , Hendrik Van PoppelHendrik Van Poppel Universitair ziekenhuis Leuven, Leuven, Belgium More articles by this author , Axel HeidenreichAxel Heidenreich Cologne University, Cologne, Germany Financial interest and/or other relationship with Astellas Pharma, Inc. More articles by this author , Peter IversenPeter Iversen Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Financial interest and/or other relationship with Astellas Pharma, Inc. More articles by this author , Johan BraeckmanJohan Braeckman Universitair ziekenhuis Brussels, Brussels, Belgium More articles by this author , Jiri HeracekJiri Heracek Univerzita Karlova v Praze, Prague, Czech Republic More articles by this author , Benoit BaronBenoit Baron Astellas Pharma, Inc., Leiden, The Netherlands Financial interest and/or other relationship with Astellas Pharma, Inc. More articles by this author , Andrew KrivoshikAndrew Krivoshik Astellas Pharma, Inc., Northbrook, Illinois Financial interest and/or other relationship with Astellas Pharma, Inc. More articles by this author , Mohammad HirmandMohammad Hirmand Medivation, Inc., San Francisco, California Financial interest and/or other relationship with Pfizer, Inc. and Medivation, Inc. More articles by this author , and Matthew R. SmithMatthew R. Smith Massachusetts General Hospital Cancer Center, Boston, Massachusetts More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.08.103AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: A phase 2 study of enzalutamide monotherapy in patients with hormone naïve prostate cancer demonstrated high prostate specific antigen response rates at 25 weeks, 1 year and 2 years with minimal effects on total body bone mineral density and favorable safety. In this followup analysis we evaluated enzalutamide antitumor activity and safety at 3 years. Materials and Methods: In a single arm analysis 67 patients with hormone naïve prostate cancer and noncastrate testosterone (230 ng/dl or greater) received enzalutamide 160 mg per day orally until disease progression or unacceptable toxicity. The primary end point was the prostate specific antigen response (80% or greater decline from baseline). Results: No patients discontinued treatment during year 3. Of 42 patients with prostate specific antigen assessments at 3 years 38 (90.5%, 95% CI 77.4–97.3) maintained a prostate specific antigen response. Of 26 patients with metastases at baseline 17 (65.4%) had a complete or partial response as the best overall response during 3 years. In patients who completed the 3-year visit minimal mean changes from baseline were observed in total body bone mineral density or bone mineral density of the femoral neck, trochanter, spine L1–L4 or forearm (range –2.7% to –0.1%). At 3 years total body fat had increased a mean of 16.5%, total lean body mass had decreased a mean of –6.5% and global health status had minimally decreased from baseline. Common adverse events were gynecomastia, fatigue, hot flush and nipple pain. Conclusions: Enzalutamide antitumor activity was maintained in patients with hormone naïve prostate cancer at 3 years. Overall bone mineral density, global health status and safety results were similar to those at 2 years. References 1 : Guidelines on prostate cancer. Updated March 2016. European Association of Urology. Available at http://uroweb.org/guideline/prostate-cancer/. Accessed February 28, 2017. Google Scholar 2 : NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)—Prostate Cancer 2016. Updated 2016. Available at http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed March 23, 2017. Google Scholar 3 : Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer2009; 115: 2388. Google Scholar 4 : Androgen deprivation therapy in the treatment of advanced prostate cancer. Rev Urol2007; 9: S3. Google Scholar 5 : Risk of fracture in men with prostate cancer on androgen deprivation therapy: a population-based cohort study in New Zealand. BMC Cancer2015; 15: 837. Google Scholar 6 : Quantifying the evidence for the risk of metabolic syndrome and its components following androgen deprivation therapy for prostate cancer: a meta-analysis. PLoS One2015; 10: e0117344. Google Scholar 7 : Quantifying observational evidence for risk of fatal and nonfatal cardiovascular disease following androgen deprivation therapy for prostate cancer: a meta-analysis. Eur Urol2015; 68: 386. Google Scholar 8 : A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol1998; 33: 447. Google Scholar 9 : Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup. J Urol2000; 164: 1579. Link, Google Scholar 10 : Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med2012; 367: 1187. Google Scholar 11 : Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med2014; 371: 424. Google Scholar 12 : Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol2016; 17: 153. Google Scholar 13 : Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science2009; 324: 787. Google Scholar 14 : Enzalutamide versus bicalutamide in castration-resistant prostate cancer: the STRIVE trial. J Clin Oncol2016; 34: 2098. Google Scholar 15 : Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Lancet Oncol2014; 15: 592. Google Scholar 16 : Long-term efficacy and safety of enzalutamide monotherapy in hormone-naive prostate cancer: 1- and 2-year open-label follow-up results. Eur Urol2015; 68: 787. Google Scholar 17 : Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med2005; 352: 154. Google Scholar 18 : Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol2003; 169: 2008. Link, Google Scholar 19 : Progressive osteoporosis during androgen deprivation therapy for prostate cancer. J Urol2000; 163: 181. Link, Google Scholar 20 : Bone mineral density in men treated with synthetic gonadotropin-releasing hormone agonists for prostatic carcinoma. J Urol1999; 161: 1219. Link, Google Scholar 21 : Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med2001; 345: 948. Google Scholar 22 : Bicalutamide 150 mg maintains bone mineral density during monotherapy for localized or locally advanced prostate cancer. J Urol2004; 171: 2272. Link, Google Scholar 23 : Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab2002; 87: 599. Crossref, Medline, Google Scholar 24 : Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol2004; 22: 2546. Google Scholar © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byTaneja S (2019) Re: Enzalutamide with Standard First-Line Therapy in Metastatic Prostate CancerJournal of Urology, VOL. 203, NO. 1, (32-33), Online publication date: 1-Jan-2020.Taneja S (2019) Re: Darolutamide in Nonmetastatic, Castration-Resistant Prostate CancerJournal of Urology, VOL. 202, NO. 4, (660-661), Online publication date: 1-Oct-2019. Volume 199Issue 2February 2018Page: 459-464Supplementary Materials Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.Keywordsprostate-specific antigenMDV 3100bone densityprostatic neoplasmsdrug related side effects and adverse reactionsAcknowledgmentsDr. Charlene Rivera and Lauren Smith, Complete HealthVizion, provided medical writing and editorial support.MetricsAuthor Information Bertrand Tombal Cliniques universitaires Saint-Luc, Brussels, Belgium Financial interest and/or other relationship with Astellas Pharma, Inc., Pfizer, Inc. and Medivation, Inc. More articles by this author Michael Borre Aarhus University Hospital, Aarhus, Denmark More articles by this author Per Rathenborg Herlev Hospital, Herlev, Denmark More articles by this author Patrick Werbrouck AZ Groeninge Kortrijk, Kortrijk, Belgium More articles by this author Hendrik Van Poppel Universitair ziekenhuis Leuven, Leuven, Belgium More articles by this author Axel Heidenreich Cologne University, Cologne, Germany Financial interest and/or other relationship with Astellas Pharma, Inc. More articles by this author Peter Iversen Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Financial interest and/or other relationship with Astellas Pharma, Inc. More articles by this author Johan Braeckman Universitair ziekenhuis Brussels, Brussels, Belgium More articles by this author Jiri Heracek Univerzita Karlova v Praze, Prague, Czech Republic More articles by this author Benoit Baron Astellas Pharma, Inc., Leiden, The Netherlands Financial interest and/or other relationship with Astellas Pharma, Inc. More articles by this author Andrew Krivoshik Astellas Pharma, Inc., Northbrook, Illinois Financial interest and/or other relationship with Astellas Pharma, Inc. More articles by this author Mohammad Hirmand Medivation, Inc., San Francisco, California Financial interest and/or other relationship with Pfizer, Inc. and Medivation, Inc. More articles by this author Matthew R. Smith Massachusetts General Hospital Cancer Center, Boston, Massachusetts More articles by this author Expand All Advertisement PDF downloadLoading ...