PD28-01 TESTOSTERONE LOWERING, PSA RESPONSE AND QUALITY OF LIFE IN PATIENTS WITH ADVANCED HORMONE SENSITIVE PROSTATE CANCER RECEIVING TAK-385, AN ORAL GNRH ANTAGONIST: PHASE 2 INTERIM ANALYSIS (2016)

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) I1 Apr 2016PD28-01 TESTOSTERONE LOWERING, PSA RESPONSE AND QUALITY OF LIFE IN PATIENTS WITH ADVANCED HORMONE SENSITIVE PROSTATE CANCER RECEIVING TAK-385, AN ORAL GNRH ANTAGONIST: PHASE 2 INTERIM ANALYSIS Neal D. Shore, James L. Bailen, Christopher Pieczonka, Daniel R. Saltzstein, Paul R. Sieber, David B. MacLean, Hongliang Shi, Hélène M. Faessel, Huamao Mark Lin, Yanyan Zhu, and Fred Saad Neal D. ShoreNeal D. Shore More articles by this author , James L. BailenJames L. Bailen More articles by this author , Christopher PieczonkaChristopher Pieczonka More articles by this author , Daniel R. SaltzsteinDaniel R. Saltzstein More articles by this author , Paul R. SieberPaul R. Sieber More articles by this author , David B. MacLeanDavid B. MacLean More articles by this author , Hongliang ShiHongliang Shi More articles by this author , Hélène M. FaesselHélène M. Faessel More articles by this author , Huamao Mark LinHuamao Mark Lin More articles by this author , Yanyan ZhuYanyan Zhu More articles by this author , and Fred SaadFred Saad More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.388AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES TAK-385 is an investigational, oral, non-peptide GnRH antagonist in late phase 2 evaluation for the management of hormone sensitive prostate cancer (HSPC). Two trials are ongoing: TAK-385 120 mg daily (QD) vs degarelix for patients (pts) requiring 6-mos neoadjuvant/adjuvant to EBRT (NCT02135445) and continuous TAK-385 80 or 120 mg QD vs leuprorelin (LEU) for advanced PC (relapse post local treatment or M1; NCT02083185; reported here). METHODS Pts aged ≥18 yrs with biopsy-confirmed PC, baseline testosterone (T) >150 ng/dL and PSA >2 ng/mL, and candidates for first-line androgen deprivation therapy, were randomized to receive oral TAK-385, 80 or 120 mg, QD or LEU 22.5 mg SC Q12 wks, for 48 wks. The primary endpoint was effective castration rate (T <50 ng/dL) at all scheduled visits from wk 5-24. Secondary endpoints included safety, PK, PSA response and quality of life (QoL). RESULTS At the second interim analysis (May 2015), 92% of 75 pts in the 2 TAK-385 arms (median age 73 yrs) achieved sustained castration rates (wk 5-24) vs 95% of 20 pts in the LEU arm (median age 68.5 yrs). Median T levels after 3 days of TAK-385 fell to castrate levels (36.9 ng/dL) vs the expected T flare (648.1 ng/dL) with LEU. After 2 wks, median T with TAK-385 achieved castration levels of <20 ng/dL and from wk 5-24 most pts in all arms maintained median T~10 ng/ dL. Consistent with the onset and depth of T lowering, PSA50 after 4 wks was 81% (TAK-385) and 20% (LEU). After 24 wks, median PSA reduction was 97.3% (0.1 ng/mL, TAK-385) vs 92.4% (0.2 ng/mL, LEU). Global QoL scores after 24 wks were similar across arms (mean decrease of 6.9 points [p=0.004] from baseline score of 81.4 for TAK-385 vs 7.4 points [p=0.131] from 79.6 for LEU. Most pronounced, significant changes from baseline occurred in 2 EORTC QLQ-PR25 subscales (sexual activity and hormonal-treatment related symptoms) and were similar across arms. TAK-385 safety profile is consistent with medical castration with to date no identified significant off-target toxicity. All-grade adverse events occurred in 91% vs 95% pts (TAK-385 vs LEU); the most common were hot flush (59/60%) and fatigue (21/15%). PK analysis showed dose-proportional plasma trough levels over >6 mos consistent with phase 1 results. CONCLUSIONS As a GnRH antagonist with rapid T and PSA response, the long term tolerability, efficacy and QoL of TAK-385 appear comparable to LEU. A phase 3 study of TAK-385, as an option to injectable GnRH therapies for PC pts, is planned. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e654 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Neal D. Shore More articles by this author James L. Bailen More articles by this author Christopher Pieczonka More articles by this author Daniel R. Saltzstein More articles by this author Paul R. Sieber More articles by this author David B. MacLean More articles by this author Hongliang Shi More articles by this author Hélène M. Faessel More articles by this author Huamao Mark Lin More articles by this author Yanyan Zhu More articles by this author Fred Saad More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...