Journal article
Phase 2 Trial of GTx-758, an Estrogen Receptor Alpha Agonist, in Men With Castration-Resistant Prostate Cancer
Clinical genitourinary cancer, v 18(6), pp 436-443
Dec 2020
PMID: 32321673
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Novel estrogen therapy has the potential to be efficacious, with a favorable adverse event profile, in castration-resistant prostate cancer (CRPC). We performed a phase 2 trial to assess the ability of GTx-758, an oral selective estrogen receptor alpha agonist, to result in a ≥ 50% PSA decline by day 90, modulate free testosterone and sex hormone–binding globulin (SHBG) levels, and affect estrogen deficiency adverse events.
CRPC patients received GTx-758 in two dose cohorts, 125 and 250 mg/d. The primary endpoint was the proportion of subjects who experienced a ≥ 50% PSA decline by day 90. Secondary endpoints included changes in testosterone, SHBG, bone turnover markers, and hot flashes, as well as safety.
Four (10.5%) of 38 (95% CI, 2.9, 24.8; P = .120) and 10 (25.6%) of 39 patients (95% CI, 13.0, 42.1; P < .001) in the GTx-758 125 and 250 mg/d cohorts, respectively, experienced ≥ 50% PSA decline. SHBG was increased, providing a mechanism for notable decreases in free testosterone. In the 250 mg/d cohort, 9 men presented with moderate to severe hot flashes, and after 12 weeks, 4 (44%) of 9 reported either mild or no hot flashes (P = .001). The rate of venous thromboembolic events was 0% and 5.1% in the 125 and 250 mg/d arms, respectively.
GTx-758 has clinical activity for CRPC in a dose-dependent fashion. GTx-758 resulted in a reduction in hot flashes. On the basis of these findings, further clinical investigation of novel estrogen therapies is warranted.
An open-label phase 2 trial was performed to assess the ability of GTx-758, an oral selective estrogen receptor alpha agonist, to induce a ≥ 50% decrease in prostate-specific antigen (PSA) decline by day 90, modulate free testosterone and sex hormone–binding globulin (SHBG) levels, and affect estrogen deficiency–related adverse events in men with castratation-resistant prostate cancer. The 250 mg/d cohort met statistical significance for the PSA decline rate. SHBG levels were increased, there were beneficial effects on hot flashes, and there was a minimal rate of venous thromboembolic events.
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Details
- Title
- Phase 2 Trial of GTx-758, an Estrogen Receptor Alpha Agonist, in Men With Castration-Resistant Prostate Cancer
- Creators
- Evan Y. Yu - Fred Hutch Cancer CenterMichael L. Hancock - GTx Inc, Memphis, TNWilliam Aronson - University of California, Los AngelesThomas Flaig - University of Colorado BoulderLaurence Belkoff - Urology AssociatesRonald Tutrone - Chesapeake Urology AssociatesRyan Taylor - University of California, Los AngelesPatrick C. Hardigan - Nova Southeastern UniversityRobert H. Getzenberg - Nova Southeastern University
- Publication Details
- Clinical genitourinary cancer, v 18(6), pp 436-443
- Publisher
- Elsevier
- Number of pages
- 8
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Web of Science ID
- WOS:000604256200004
- Scopus ID
- 2-s2.0-85083302216
- Other Identifier
- 991021916909204721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Oncology
- Urology & Nephrology