Testosterone (T) suppression by weight and age groups in four pivotal trials of in-situ forming polymer-delivered, subcutaneously administered leuprolide acetate in men with prostate cancer (PCa).

Abstract

172 Background: In-situ forming polymer-delivered, subcutaneous leuprolide acetate (SC-LA) has previously been shown to suppress serum T levels to ≤20ng/dL in advanced PCa patients. Currently, luteinizing hormone releasing hormone agonists are dosed independently of body weight (BW) or age. Reaching nadir T<20ng/dL within the first year of androgen deprivation therapy (ADT) is associated with improved clinical outcomes such as time to progression and disease specific survival (Klotz 2015). As maintaining castrate T levels during ADT is important, it is of interest to understand if factors such as BW or age should be considered when selecting a therapy. This study aims to determine if patient BW and age correlate with the pharmacodynamic profile of all SC-LA formulations. Methods: In 4 open-label, prospective single-arm, fixed dose, pivotal studies, 438 PCa patients were treated with either 7.5, 22.5, 30, or 45mg SC-LA lasting 1, 3, 4, or 6 months. Blood was sampled at screening, baseline, 2, 4, 8 hours post dosing, day 1, 2, 3, 7, and every other week until end of study and assayed for total T by radioimmunoassay. Results: Mean BW of 86 kg (range 49-146) and age of 73 years (range 40-86) was similar across the 4 studies. >90% of patients in all age groups (including 100% of those <60 years) and ≥92% of patients in all BW groups (including 97% of those ≥90 kg) achieved T≤50ng/dL by week 4. When pooled, all age and BW groups achieved median T≤20ng/dL by week 4 and maintained until the end of the study (Table). Conclusions: The results demonstrate that all SC-LA dose formulations consistently achieve and maintain T≤20ng/dL across all BW and age subgroups, including those with the highest BW (>90 kg) and youngest age (<70 years). BW and age do not appear to have an impact on consistent drug delivery and T suppression by SC-LA. Consistent achievement of T ≤20ng/dL may have implications for improved clinical outcomes and progression free survival in PCa patients. [Table: see text]