Onset and maintenance of testosterone suppression in four pivotal trials of subcutaneously administered leuprolide acetate formulated with in-situ forming polymeric delivery technology.

Abstract

205 Background: Subcutaneously administered leuprolide acetate (SC-LA) formulated with in-situ forming polymeric delivery technology has demonstrated efficacy in suppressing testosterone (T) levels to achieve and maintain medical castration in patients with advanced prostate cancer (PCa). Increasing evidence suggests that reaching and sustaining the lowest T possible is desirable and correlated with disease specific survival. Data was pooled from four pivotal trials to determine the onset and maintenance of T levels at or lower than castration with SC-LA treatment. Methods: Eugonadal PCa patients received either 7.5 (6 doses), 22.5, 30, 45 mg (2 doses each) injections of SC-LA lasting 1, 3, 4, or 6 months, respectively, in 4 open-label, fixed-dose, pivotal trials. Serum T levels were assessed at screening, baseline (Day 0), and at least once per week throughout the studies. Target T levels were 50, 20, and 10ng/dL. The time when T crossed target level was extrapolated using the following formula: (target T – post-target T) / (pre-target T – post-target T) x (post-target date – pre-target date) = estimated days between crossing target T and post-target measurement Results: In the pooled population (N=437), median onset of T ≤50, ≤20, and ≤10ng/dL were 21 days, 28 days, and 35 days, respectively. Once the target T level was achieved, the mean proportion of time that patients maintained T suppression below each target level was 100% for T≤50 ng/dL, 94-99% for T≤20ng/dL, and 66-85% for T≤10ng/dL (Table). Conclusions: SC-LA achieved rapid onset of T≤50ng/dL in 3 weeks, T≤20ng/dL in 4 weeks, and T≤10ng/dL in 5 weeks. SC-LA maintained consistently low T levels, with over 66%, 95%, and 100% of the treatment period remaining below 10, 20, and 50 ng/dL respectively. This T suppression profile may have relevance for improved patient survival and extended time to disease progression. [Table: see text]