MP87-16 NOVEL ANTIANDROGEN ARN-509 IN HIGH-RISK NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER

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You have accessJournal of UrologyProstate Cancer: Advanced III1 Apr 2015MP87-16 NOVEL ANTIANDROGEN ARN-509 IN HIGH-RISK NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER Neal D. Shore, Emmanuel S. Antonarakis, Charles J. Ryan, William R. Berry, Glenn Liu, Celestia Higano, Edna Chow Maneval, Rajesh Bandekar, Carla J. de Boer, Mary B. Todd, Margaret K. Yu, Dana E. Rathkopf, and Matthew R. Smith Neal D. ShoreNeal D. Shore More articles by this author , Emmanuel S. AntonarakisEmmanuel S. Antonarakis More articles by this author , Charles J. RyanCharles J. Ryan More articles by this author , William R. BerryWilliam R. Berry More articles by this author , Glenn LiuGlenn Liu More articles by this author , Celestia HiganoCelestia Higano More articles by this author , Edna Chow ManevalEdna Chow Maneval More articles by this author , Rajesh BandekarRajesh Bandekar More articles by this author , Carla J. de BoerCarla J. de Boer More articles by this author , Mary B. ToddMary B. Todd More articles by this author , Margaret K. YuMargaret K. Yu More articles by this author , Dana E. RathkopfDana E. Rathkopf More articles by this author , and Matthew R. SmithMatthew R. Smith More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1961AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES ARN-509 selectively binds the androgen receptor and impairs its nuclear translocation and DNA binding to androgen response elements. Study ARN-509-001 evaluates ARN-509 activity in pts with high-risk nonmetastatic (M0) castration-resistant prostate cancer (CRPC), chemotherapy-naïve metastatic CRPC (mCRPC), and mCRPC post abiraterone acetate. We report the updated results for the M0 CRPC cohort as of February 2014. METHODS All pts had CRPC with no radiographic evidence of metastases (pelvic lymph nodes < 3 cm below the iliac bifurcation were allowed) and high risk for disease progression based on prostate-specific antigen (PSA) ≥ 8 ng/mL within 3 mos of enrollment and/or PSA doubling time (PSADT) ≤ 10 mos. All pts received ARN-509 240 mg/d. Primary end point: PSA response at 3 mos according to Prostate Cancer Working Group 2 (PCWG2) criteria. Secondary end points: safety, time to PSA progression, and metastasis-free survival (MFS). PSA was measured every month and tumor imaging was performed every 4 mos. RESULTS M0 CRPC cohort enrolled 51 pts from Nov 2011 to Jun 2012; 4 pts had metastatic disease and were excluded from the efficacy analysis. Median age was 71 years (range 51-88). Baseline characteristics were ECOG performance status 0 (76%); Gleason score ≤ 7 (57%); median PSA 10.7 ng/mL (range 0.5-201.7); and PSADT ≤ 10 mos (45%). All pts received prior treatment with a luteinizing hormone–releasing hormone analog. Forty-one pts (80%) also received a first-generation antiandrogen. At median follow-up of 20.2 mos, 29 (57%) pts remain on study. Pts discontinued due to disease progression (n = 7), adverse events (AEs) (n = 7), withdrew consent (n=3), or other reasons (n = 5). Most AEs were grade 1 or 2. Most common treatment-emergent AEs (all grades; grade ≥ 3): fatigue (57%; 4%), diarrhea (41%; 2%), nausea (29%; 0%), dysgeusia (20%; 0%), arthralgia (18%; 2%), and weight decreased (16%; 2%). The incidence of hypertension was low (10%; 2%). No seizures were reported. Other central nervous system events: headaches (10%; 0%), falls (4%; 0%), and hallucinations (0%). CONCLUSIONS ARN-509 is well tolerated in pts with high-risk M0 CRPC, with anti-tumor activity based on durable PSA response and delayed disease progression. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1090 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal D. Shore More articles by this author Emmanuel S. Antonarakis More articles by this author Charles J. Ryan More articles by this author William R. Berry More articles by this author Glenn Liu More articles by this author Celestia Higano More articles by this author Edna Chow Maneval More articles by this author Rajesh Bandekar More articles by this author Carla J. de Boer More articles by this author Mary B. Todd More articles by this author Margaret K. Yu More articles by this author Dana E. Rathkopf More articles by this author Matthew R. Smith More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...