Oncology - Prostate
Introduction & Objective : Subcutaneously administered leuprolide acetate (SC-LA) formulated with a biodegradable polymer delivery system has demonstrated efficacy in suppressing testosterone (T) levels to achieve and maintain medical castration (T < 50 ng/dL) in patients with advanced prostate cancer (PCa). Increasing evidence suggests that reaching and sustaining the lowest T possible is desirable during androgen deprivation therapy and correlates with disease specific survival. Data were pooled from four 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 was measured 2-4 times on day 0 and once on days 1, 2, 3, 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%, 94-99%, and 66-85% for T ≤ 50, 20, and 10 ng/dL respectively (Table).
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.