Background: In prostate cancer therapy, achieving and maintaining effective testosterone (T) suppression to the level attained with surgical castration is the cornerstone of androgen deprivation therapy (ADT). Subcutaneously administered leuprolide acetate (SC-LA) formulated with a biodegradable polymer delivery system has demonstrated efficacy in suppressing T levels to achieve and maintain medical castration (T <50 ng/dL) in patients with advanced prostate cancer (PCa). However, <20 ng/dL may be a more appropriate standard for T castration level compared with <50 ng/dL. Increasing evidence suggests that reaching and sustaining the lowest T level possible is desirable during ADT and correlates with disease-specific survival. Therefore, lowering the T level as much as possible should be the goal of ADT in patients with metastatic PCa.
Objective: Data were pooled from 4 pivotal trials to determine the onset and maintenance of T levels at or lower than castrate levels with SC-LA treatment.
Methods: Eugonadal PCa patients received either 7.5- (6 doses), 22.5-, 30-, or 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. T level was measured 2 to 4 times on day 0 and once on days 1, 2, 3, and 7 and every week until the next dose through the end of the studies; the 45-mg group had an additional measurement taken on day 2. Target T levels were 50, 20, and 10 ng/dL. The onset of T suppression and the proportion of time serum T remained below the target levels were calculated for each patient by extrapolating the time point when T first crossed the target. Proportion of time below target was calculated as total time T remained below target divided by time after target first achieved to end of study.
Results: In the pooled population (N = 437), median onset of T levels ≤50, ≤20, and ≤10 ng/dL were 21, 28, and 35 days, respectively. Once target T was achieved, the mean proportion of time that patients maintained T suppression below each target level was 100%, 94% to 99%, and 66% to 85% for T ≤50, 20, and 10 ng/dL, respectively.
Conclusions: SC-LA achieved effective onset of T ≤50, ≤20, and ≤10 ng/dL at 3, 4, and 5 weeks, respectively. SC-LA maintained consistently low T levels, with over 66% and 94% of the treatment period remaining below 10 and 20 ng/dL, and 100% of the treatment period remaining below 50 ng/dL. This T suppression profile may have implications for improved patient survival and extended time to disease progression.
Disclosures: Sponsor: Tolmar, Inc. Previously presented at ASCO Genitourinary Cancer Symposium 2018.