647 PHASE 1–2 STUDY OF MDV3100 IN PRE- AND POST-DOCETAXEL ADVANCED PROSTATE CANCER: LONG-TERM EFFICACY RESULTS

Abstract

You have accessJournal of UrologyProstate Cancer: Advanced1 Apr 2011647 PHASE 1–2 STUDY OF MDV3100 IN PRE- AND POST-DOCETAXEL ADVANCED PROSTATE CANCER: LONG-TERM EFFICACY RESULTS Celestia Higano, Tomasz Beer, Evan Yu, Mary-Ellen Taplin, Eleni Efstathiou, Aseem Anand, Mohammad Hirmand, Martin Fleisher, and Howard Scher Celestia HiganoCelestia Higano Seattle, WA More articles by this author , Tomasz BeerTomasz Beer Portland, OR More articles by this author , Evan YuEvan Yu Seattle, WA More articles by this author , Mary-Ellen TaplinMary-Ellen Taplin Boston, MA More articles by this author , Eleni EfstathiouEleni Efstathiou Houston, TX More articles by this author , Aseem AnandAseem Anand New York, NY More articles by this author , Mohammad HirmandMohammad Hirmand San Francisco, CA More articles by this author , Martin FleisherMartin Fleisher New York, NY More articles by this author , and Howard ScherHoward Scher New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1549AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES MDV3100 is a novel androgen receptor (AR) antagonist with activity against prostate cancer (PCa) cells that overexpress AR. MDV3100 slows growth and induces cell death in bicalutamide-resistant tumors via 3 complementary actions: AR direct antagonism, inhibition of nuclear translocation of the AR complex, and inhibition of DNA binding by the AR (Tran C et al. Science. 2009;324:787). AR partial agonism has not been seen with MDV3100 in vitro. Preliminary antitumor activity and adverse events have been reported in advanced PCa from a phase 1–2 study of MDV3100 (Scher HI et al. Lancet. 2010;375:1437). Long-term follow-up for time to prostate-specific antigen (PSA) and radiographic progression from this study are presented here. METHODS Patients (pts) with progressive castration-resistant PCa were enrolled in sequential cohorts of 3–6 pts; MDV3100 doses were 30, 60, 150, 240, 360, 480, and 600 mg/day. After confirming dose tolerability, enrollment was expanded for doses ≥60 mg/day to include approximately 24 pts per dose cohort who were chemotherapy-naive (chemo-naive; n=12) or previously treated with docetaxel (post-chemo; n=12). RESULTS 140 pts were enrolled, 18 (13%) of whom continue on active treatment (chemo-naive, n=16; post-chemo, n=2) with a median of 131 weeks of therapy. The median time on treatment is 51 weeks for chemo-naive (n=65) and 17 weeks for post-chemo (n=75) pts. The median time to PSA progression, defined as a ≥25% increase in PSA from baseline, was not met for chemo-naive pts and was 33 weeks for post-chemo pts. Median time to PSA progression by Prostate Cancer Clinical Trials Working Group 2 criteria was 41 and 20 weeks for chemo-naive and post-chemo pts, respectively. Median time to radiological progression is shown in the Figure. CONCLUSIONS In this phase 1–2 study, MDV3100 demonstrated durable antitumor activity in chemo-naive and post-chemo pts with advanced PCa. To confirm these promising results, MDV3100 is being evaluated in 2 ongoing global phase 3 studies in pts with advanced progressive PCa: the AFFIRM study in pts previously treated with docetaxel, and the PREVAIL study in asymptomatic or mildly symptomatic chemo-naive pts who have progressed following androgen deprivation therapy. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e262 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Celestia Higano Seattle, WA More articles by this author Tomasz Beer Portland, OR More articles by this author Evan Yu Seattle, WA More articles by this author Mary-Ellen Taplin Boston, MA More articles by this author Eleni Efstathiou Houston, TX More articles by this author Aseem Anand New York, NY More articles by this author Mohammad Hirmand San Francisco, CA More articles by this author Martin Fleisher New York, NY More articles by this author Howard Scher New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...