Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies

INTRODUCTION Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to "castrate" levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels. METHODS In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks. RESULTS Pooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks. CONCLUSION Both 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted.