Session: SAT 292-325-Breast & Prostate Cancer
Poster Board SAT-319
Objectives: Herein we compare the effects GTx-758 (an oral, selective estrogen receptor alpha (ERα) agonist) versus leuprolide on total T, free (unbound) serum T, SHBG and PSA levels in men with advanced prostate cancer.
Methods: In Phase II studies, men with advanced prostate cancer (n=164) received 1000 mg or 2000 mg GTx-758 daily or Lupron Depot® (4 month), while men with CRPC (n=7) received 2000 mg GTx-758 daily while on ADT. Serum concentrations of total T, free T, PSA and SHBG were determined at baseline and during treatment.
Results: The ADT naïve ITT population receiving GTx-758 demonstrated a mean reduction in serum total T from baseline of 54±52 and 72±43% for the 1000 and 2000 mg doses, respectively, compared to 93±2.8% reduction in the Lupron treated arm at Day 21. However, mean PSA reductions from baseline at Day 21 were 55±47 and 60±32% for the 1000 and 2000 mg doses of GTx-758, respectively, compared to 38±24% in Lupron treated patients. GTx-758 treatment resulted in 55 and 51% greater reduction in serum free T per unit reduction in serum total T relative to Lupron in the 1000 mg and 2000 mg arms, respectively, at Day 21. Reductions in serum free T coincided with mean increases in SHBG of 399±186 and 439±165% for 1000 mg and 2000 mg GTx-758 groups, respectively, compared to 5±14% in Lupron treated patients at Day 28. SHBG inductions were highly correlated with reductions in %Free T([free T/total T]X100) in both ADT naïve and CRPC prostate cancer patients (p<0.001).
Conclusions: Although GTx-758 and LHRH ADT, both reduce total serum T and PSA levels in ADT naïve advanced prostate cancer patients, SHBG induction rapidly reduced %free T to a greater degree in only the GTx-758 treated patients. GTx-758 therapy also demonstrated efficacy in men with CRPC, with similar reductions in %free T and PSA observed. The ability of GTx-758 to reduce free T demonstrates a unique and effective mechanism to treat men with advanced prostate cancer and CRPC.
Source of Funding: GTx, Inc.
Disclosure: CCC: Employee, GTx INC, Employee, GTx INC. RHG: Employee, GTx INC, Employee, GTx INC. MSS: Chairman, GTx INC, Chairman, GTx. JTD: Chief Scientific Officer, GTx, Inc., Chief Scientific Officer, GTx, Inc..
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