Login to Access Video or Poster Abstract: MP57-17
Sources of Funding: TOLMAR, Inc.

Introduction

Prostate cancer patients receive androgen deprivation therapy (ADT) to suppress testosterone (T) to prevent proliferation of cancer cells. T suppression levels achieved by bilateral orchiectomy remain the gold standard for the target of suppression by ADT. Although the historical threshold definition of castration is T ≤50 ng/dL, increasing evidence suggests a T lower than 20 ng/dL may improve clinical outcomes, e.g., increased cancer specific survival and delayed disease progression. However, it has not been established what level of serum LA is required to achieve T suppression below this more rigorous threshold. To determine the level of serum leuprolide required to maintain level T suppression ≤20 ng/dL in prostate cancer patients, data from 4 pivotal trials evaluating long-acting, subcutaneously (SC) administered leuprolide acetate (LA) formulated with a biodegradable polymer were pooled.

Methods

438 eugonadal prostate cancer patients (age 40-86) were treated with SC-LA 7.5, 22.5, 30, or 45mg delivered with a single dose lasting over 1, 3, 4, or 6 months (n=120, 117, 90, 111), respectively in 4 open-label, fixed-dose, pivotal trials. Descriptive statistics were used to summarize the median concentration of leuprolide acetate at each time point as well as to determine level of T suppression.

Results

Over the dosing intervals of the 1, 3, 4 and 6-month SC-LA formulations, median serum leuprolide levels were consistent. In the pooled analysis (n=66 with PK assessments), 60(91%) patients with LA ≥0.1 ng/mL achieved T ≤20 ng/dL by week 5. Of all patients (n=438), 90-96% achieved T ≤20 ng/dL by week 6 and 90-97% maintained T ≤20 ng/dL from weeks 6-24.

Conclusions

These data suggest that SC-LA achieves consistent and prolonged drug delivery and that serum LA levels above 0.1 ng/mL provide favorable T suppression below 20 ng/dL. Consistent achievement of these levels may have implications for improved clinical outcomes, e.g., increased cancer specific and progression free survival.

Funding

TOLMAR, Inc.