OBJECTIVES: Everolimus plus exemestane (EVE+EXE) recently received approval for the treatment of patients with HR+/HER2- advanced breast cancer that recurs or progresses during/after non-steroidal aromatase inhibitors. This study was designed to evaluate the expected costs of managing adverse events during EVE+EXE therapy and single-agent chemotherapy in the western European region. METHODS: An economic model was developed to estimate per-patient cost of managing adverse events for patients receiving EVE+EXE or chemotherapies. Adverse event rates for EVE+EXE were collected from the phase III BOLERO-2 trial. Adverse event rates for capecitabine, docetaxel, and doxorubicin chemotherapies were collected from published clinical trial data. Grade 3/4 adverse events with at least 2% prevalence during any of these treatments were included in the study. The adverse event rate estimates do not count multiple episodes of the same event. Costs of managing each adverse event were obtained from the literature and averaged across western European countries (United Kingdom, Germany, France, Italy, Belgium, Spain, Sweden, and Switzerland), where available. The costs were inflated to 2012 Euros (€). RESULTS: Expected per-patient costs of managing adverse events within the first year of treatment among patients with advanced breast cancer receiving EVE+EXE were €730. Among patients receiving capecitabine, docetaxel, or doxorubicin as single-agent chemotherapy, expected per-patient costs were €1721, €2390, and €1230, respectively. The most costly adverse event for patients treated with EVE+EXE was anemia (€152 per patient). The most costly adverse event for patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively. CONCLUSIONS: Expected costs of managing adverse events in patients with HR+/HER2- advanced breast cancer receiving EVE+EXE are about one-half to one-third of the costs for those receiving chemotherapies. This economic consideration can have important implications for healthcare spending in the advanced breast cancer setting.