OBJECTIVES :

To characterize the potential drug-drug interactions (pDDIs) to novel anti-androgen agents (AAs) within the non-metastatic castration-resistant prostate cancer (nmCRPC) population.

METHODS :

This is a retrospective database study of the Optum Clinformatics Data Mart (administrative claims database associated with large commercial health plan) from January 1, 2017, through March 31, 2020. The study population included adult males with prostate cancer, evidence of castration, absence of metastases codes and >1 pharmacy claim for novel AA (index date). Continuous eligibility was required for 12 months prior and at least 3 months post-index. The top 50 most prevalent concomitant medications during baseline were identified and pDDIs between each of these 50 medications and novel AAs - darolutamide, enzalutamide, and apalutamide were assessed using Micromedex and Lexicomp compendia.

RESULTS :

Among 718 patients (mean age 76yrs (standard deviation [SD]: 8.3), 59% white, 81% Medicare insurance) most common medication classes were cardiovascular (85%), anti-infective (61%), and central nervous system (57%). 72% had 5 or more concomitant drugs and mean Charlson comorbidity index was 2.2 (SD 2.2). Of the 50 most prevalent co-medications, Micromedex and Lexicomp flagged: 1 pDDI each for darolutamide; 4 and 22 for enzalutamide, respectively; and 6 and 22 for apalutamide, respectively. Most identified interactions in Micromedex were rated “major”: darolutamide (n=1), enzalutamide (n=4), and apalutamide (n=4). The majority of Lexicomp interactions had risk ratings C (i.e., monitor therapy) or D (i.e., consider modification). However, 3 interactions for apalutamide were rated X (i.e., avoid combination). A pDDI was identified among 35% of nmCRPC patients on enzalutamide, 17% on apalutamide and 7% on darolutamide.

CONCLUSIONS :

nmCRPC patients are older, have high comorbidity burden and often take multiple concomitant medicines making them susceptible to pDDIs, an important consideration while selecting treatments for nmCRPC. Both compendia show more frequent severe pDDIs for enzalutamide and apalutamide than darolutamide.