GTx-758 Effective and Well Tolerated

Rancho Mirage, CA—Preliminary findings of a phase II study demonstrated that the majority of patients on an luteinizing hormone-releasing hormone (LHRH) had suboptimal levels of free testosterone (T) that were further lowered by administration of GTx-758 (Capesaris®).

Robert H. Getzenberg, PhD, and colleagues presented the results during a poster session at the South Central Section of the American Urological Association 93rd Annual Meeting. The poster was titled Low Dose GTx-758 Decreases Free Testosterone and PSA in Men with Metastatic Castration Resistant Prostate Cancer (mCRPC).

In palliative care for patients with advanced prostate cancer, LHRH agents utilized for androgen deprivation therapy (ADT) were intended to lower total T levels to those achieved by orchiectomy. The castration equivalent level was, according to the authors, “based upon the lower limits of quantitation (50 ng/dL) of outdated assays.” In updated assays, total T levels after orchiectomy are significantly lower (<20 ng/dL), with 30 to 40% of men on LHRH agonists not achieving that level.

Recent studies have found a correlation between lower T levels and improved outcomes. Further, the biologically active form of T is unbound, free T. GTx-758 is an oral estrogen receptor a agonist that increases sex hormone binding globulin (SHBG) and lowers free T levels. Side effects associated with estrogen deficiency are ameliorated with GTx-758.

Dr. Getzenberg reported on preliminary results of a phase II open label study (G200712) of GTx-758. The study included 38 men with mCRPC. Participants continued their current regimen of ADT in combination with a low dose (125 mg) of GTx-758 for at least 90 days. Men at increased risk of venous thrombolic events were excluded from the study.

Of 14 patients who completed 90 days on GTx-758, all had a greater than or equal to a 150% increase in SHBG levels. Eleven of the 14 had suboptimal castration (free T >0.7 pg/ml) at the beginning of the study, and 91% of those (n=10/11) became optimally castrated by day 90.

There was a >45% decrease in prostate-specific antigen in 4 of the 14 patients. In 71% of treated participants, hot flashes were stable or improved, and in 73%, bone turnover markers were observed. Of adverse events (AEs) reported, none were vascular related, and there were no serious AEs.

In summary, the authors said, “The majority of patients on an LHRH agonist enrolled in this phase II study had suboptimal levels of free T that were further lowered by GTx-758 administration. GTx-758 treatment resulted in stabilization and/or improvement in reported hot flashes and bone turnover, two major side effects of ADT…these preliminary findings show that 125 mg of GTx-758 has clinical effectiveness and is well tolerated.”  Clinical trial information: (NCT01615120).