Prevalence of potential drug-drug interactions among nonmetastatic castration-resistant prostate cancer patients treated with apalutamide and enzalutamide.

e18690 Background: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are often treated with concurrent medications for the management of comorbid conditions. This increases the risk of drug interactions which may lead to compromised efficacy and safety of nmCRPC therapies. This study aimed to characterize potential drug-drug interactions (pDDIs) with the novel anti-androgen (AA) agents enzalutamide (Enza) and apalutamide (Apa) in a real-world nmCRPC population. Methods: We analyzed Optum Clinformatics Data Mart, a large claims database from January 1, 2017, through March 31, 2020. The study population included adult males with prostate cancer, evidence of castration, &gt;1 pharmacy claim for Apa or Enza (index date defined as drug initiation), and without codes for metastases. Darolutamide, a more recently approved AA, was not included due to lack of data. Concomitant medications were defined as therapy with at least 1 day overlap with Apa and Enza. The top concomitant medications covering 99% of Apa and Enza population were assessed for pDDI using Micromedex, Lexicomp, and Drugs.com compendia. Results: We identified 149 Apa and 319 Enza patients with mean age 77 years across groups. The study population was primarily white (56.3% Apa; 56.7% Enza) and had Medicare insurance (81.0% Apa; 82.2% Enza). Mean Charlson comorbidity index scores were similar for each group (Apa: 2.3 [SD: 4.1]; Enza: 2.4 [SD: 2.4]). Polypharmacy was common in both groups, with the majority taking ≥5 medications (Apa: 79.8%; Enza: 75.9%). Of the co-medications included in this analysis, Micromedex, Lexicomp and Drugs.com flagged 12, 38 and 53 pDDIs for Apa, and 7, 35 and 49 pDDIs for Enza, respectively. A pDDI was identified for 35% Apa and 21% Enza patients using Micromedex and &gt;80% of Apa and Enza patients using other compendia. The pDDIs by severity and risk rating as defined by the respective compendia are shown in Table. Specifically, 4 interactions for Apa and 1 for Enza were rated X (i.e., avoid combination). Conclusions: This study finds a high prevalence of pDDIs among Apa and Enza patients signifying the need for strict monitoring while initiating these therapies. Given the high prevalence of polypharmacy and comorbidities among nmCRPC, these patients may benefit from drugs with lower interaction potential. Future real-world analyses should be conducted to characterize the clinical and economic impact of these pDDIs as well as to assess pDDI for darolutamide. [Table: see text] </jats:p

Drug–drug interaction potential among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with novel androgen receptor inhibitors

Nonmetastatic castration-resistant prostate cancer (nmCRPC) patients are often older and use concurrent medications that increase the potential for drug–drug interactions (pDDIs). This study assessed pDDI prevalence in real-world nmCRPC patients treated with apalutamide, darolutamide, or enzalutamide. Castrated prostate cancer patients without metastases prior to androgen receptor inhibitor initiation were identified retrospectively via Optum Clinformatics Data Mart claims data (8/2019–3/2021). The top 100 concomitant medications were assessed for pDDIs. Among 1,515 patients (mean age: 77 ± 8 years; mean Charlson Comorbidity Index: 3 ± 3), 340 initiated apalutamide, 112 darolutamide, and 1,063 enzalutamide. Common concomitant medication classes were cardiovascular (80%) and central nervous system (52%). Two-thirds of the patients received ≥5 concomitant medications; 30 (30/100 medications) pDDIs were identified for apalutamide and enzalutamide each and 2 (2/100 medications) for darolutamide. Most pDDIs had risk ratings of C or D, but four for apalutamide were rated X. Approximately 58% of the patients on apalutamide, 5% on darolutamide, and 54% on enzalutamide had ≥1 identified pDDI. Results showed a higher frequency of pDDIs in patients receiving apalutamide and enzalutamide vs darolutamide. The impact of these could not be determined retrospectively. DDI risk should be carefully evaluated when discussing optimal therapy for patients with nmCRPC.</p