OBJECTIVES: To evaluate clinical and economic impact of increasing denosumab use compared to zoledronic acid (ZA) in BrCa patients with BM to a MCO. METHODS: An economic model was developed to estimate clinical and economic impact to a 1-million-member US MCO of introducing denosumab as bone-targeting agent (BTA) for prevention of SREs in BrCa patients with BM. Total number of patients receiving BTA was estimated based on disease prevalence and treatment eligibility in this population. The real-world SRE rates in ZA-treated patients were derived from a large commercial database and used together with the trial-based treatment effect for denosumab versus ZA to estimate the denosumab SRE rate. Total number of SREs, total SRE management medical cost, BTA drug cost, and total cost were calculated. The impact of denosumab per-member-per-month (PMPM) at increasing utilization rates was assessed by comparing to a scenario without denosumab, i.e., all patients received ZA. Additionally, impact of annual increase in denosumab use was conducted. RESULTS: A total of 122 BrCa patients with BM received BTA. In the scenario where all eligible patients receiving ZA, an annual total number of SREs was 155. An annual denosumab use of 20%, 35% or 45% resulted in 4.5%, 7.9%, and 10.2% reduction in total SREs and 5.7%, 10.1%, and 12.9% reduction in medical costs of managing SREs, compared to all patients receiving ZA. The drug cost was partially offset by the reductions in the medical cost and the increase in total cost was minimal (2.4%-5.5%). The PMPM ranged $0.008-$0.017. Consecutive-year analysis showed $0.004 increase in PMPM with 10% denosumab utilization increase. CONCLUSIONS: Due to superior efficacy of denosumab versus ZA in SRE prevention in BrCa patients with BM, increased denosumab use results in medical cost reduction in a US MCO.  Overall, denosumab provides additional clinical value with limited budget impact.