Association of polypharmacy with acute care utilization in older adults receiving androgen receptor signaling inhibitors for metastatic prostate cancer.

518 Background: Optimal management of metastatic prostate cancer can involve complex medication regimens, often combining androgen deprivation therapy (ADT) with novel androgen receptor signaling inhibitors (ARSIs) and other supportive medications. While these new agents have revolutionized care and improved survival, older patients may be at risk for negative outcomes from polypharmacy. Methods: We used the SEER-Medicare linked data for patients aged 66 and older with de novo metastatic prostate cancer who were prescribed abiraterone, enzalutamide, or apalutamide per part D files from 2010 to 2017, corresponding with the approval date of the first ARSI in the metastatic setting. Polypharmacy was defined based on the Youden index with a cutoff of 8 or more medications, in a 6-month window prior to ARSI treatment. This cutoff was selected for its higher sensitivity compared to the traditional threshold of 5 medications, as demonstrated in a recent study. Acute care use was defined as any inpatient hospitalization or emergency visit event within 6 months after ARSI initiation. We compared demographic characteristics between those with and without polypharmacy using t-tests and chi-square tests for association. We used negative binomial regression to compute incidence rate ratios of acute care use for each model covariate. Results: A total of 2697 patients with metastatic prostate cancer on ARSIs were included in the analysis, with an average age of 75.0 years. The majority of patients were White (80.3%), married (63.1%), and had received prior ADT (85.3%). Polypharmacy was present in slightly above half (50.6%) of patients before initiation of ARSI therapy. Patients with polypharmacy (vs. without) were significantly more likely to have received prior ADT, be married, reside in the eastern US, and have more comorbidities. Polypharmacy was also associated with higher acute care use (35.6% vs. 22.9%, p < 0.001). There were no differences in age, socioeconomic status, or ARSI treatment received between those with or without polypharmacy. In multivariable analysis adjusting for the above demographic, clinical, and treatment-related covariates, polypharmacy was associated with a 59% increased incidence rate of acute care use (IRR 1.59, 95% CI 1.28–1.98, p < 0.001). Conclusions: Polypharmacy was high in this population and independently associated with increased acute care use. Our study identifies a key marker for interventions in older adults with metastatic prostate cancer who are initiating ARSI treatment, which may prevent downstream hospital utilization.