Impact of Late Dosing on Testosterone Suppression with Two Different Leuprolide Acetate Formulations: In Situ Gel and Microsphere – An Analysis of US Clinical Data

November 2020 Vol 11, No 11
Tina DeNofrio, RN, BSN, OCN
Dana-Farber Cancer Institute
Harvard Medical School
Boston, MA
Stuart N. Atkinson, MB, ChB
Tolmar Pharmaceuticals, Inc.
Buffalo Grove, IL
Deborah M. Boldt-Houle, PhD
Tolmar Pharmaceuticals, Inc.
Buffalo Grove, IL
Julia Vandross, NP-BC, BSN, MSN
Providence Saint John’s Health Center, Santa Monica, CA

Background: Luteinizing hormone-releasing hormone (LHRH) agonists are the most frequently used androgen deprivation therapy (ADT) for prostate cancer (PCa). Achieving and maintaining effective testosterone (T) suppression to levels attained with surgical castration is the cornerstone of ADT for advanced PCa. However, T may rise above castrate level (50 ng/dL) between injections, especially if a subsequent dose is delayed. A large US analysis on LHRH agonists confirmed that late dosing is common (27%), and late injections were associated with a 4 times higher T breakthrough rate and doubled mean T compared with early/on-time injections. Delivery systems should be considered, as ADT therapies are not necessarily interchangeable. Two FDA-approved forms of leuprolide acetate (LA), the most commonly used LHRH agonist in the United States, use different extended-release systems: in situ gel technology (Gel-LA, subcutaneous) and microsphere technology (Msphere-LA, intramuscular).

Objectives: To evaluate the prevalence of late dosing and comparative impact of late dosing on T suppression for Gel-LA and Msphere-LA.

Methods: An observational analysis of US oncology and urology electronic medical records (January 1, 2007-June 30, 2016) of PCa patients who received Gel-LA or Msphere-LA injections evaluated frequency of late dosing (occurring after day 32, 97, 128, 194 for 1-, 3-, 4-, 6-month formulations, respectively), least-square mean (LSmean) T, and rate of T tests >50 ng/dL with late dosing.

Results: 2038 patients received Gel-LA and 8360 received Msphere-LA. Twenty-seven percent of injections for both drugs were late. When dosing was late, LSmean T was 48 ng/dL (Gel-LA) versus 76 ng/dL (Msphere-LA). T values were >50 ng/dL in 18% (Gel-LA) versus 25% (Msphere-LA) (odds ratio = 1.5; 95% CI, 1.1-2.0). Both of these analyses were statistically significant.

Conclusions: Overall, more than a quarter of injections were late. When dosing was late, Gel-LA was more effective than Msphere-LA at achieving and maintaining T suppression, as Gel-LA was 1.5 times more likely to have T below 50 ng/dL and had lower mean T than Msphere-LA. Although modifying clinical practice procedures to increase adherence to dosing schedules is recommended, late injections are ubiquitous in real-world practice. As higher T levels, including T escapes, have potential to adversely impact disease progression and survival, clinicians should reassess their dosing schedule adherence policies and utilize an ADT that optimizes the goal of effective T suppression.

Source of Funding: Tolmar Pharmaceuticals, Inc.

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Last modified: August 10, 2023

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