Abstract
OBJECTIVES: This study evaluates the efficiency and budgetary impact of trastuzumab deruxtecan (T-DXd) compared with standard therapy in previously treated HER2-low advanced or metastatic breast cancer, from the perspective of the Spanish National Health System. METHODS: A partitioned survival model was developed using data from the DESTINY-BREAST04 trial. Health outcomes were measured in quality-adjusted life years (QALYs) for both the overall population and the hormone receptor-positive (RH+) subgroup. The analysis was conducted from the perspective of the Spanish National Health System over a 75-month time horizon. A univariate sensitivity analysis was performed to explore parameter uncertainty. Costs were derived from Spanish healthcare databases and expert input. RESULTS: At 75 months, for the overall patient population, the total healthcare cost for patients treated with T-DXd was €201,328.27, compared with €64,654.80 with standard therapy. T-DXd provided 1.24 QALYs (2.24 life years), while standard therapy provided 1.03 QALYs (1.86 life years). The incremental cost-utility ratio (ICUR) for T-DXd compared with standard of care (SOC) was €648,710.32/QALY. For the hormone receptor-positive (RH+) subgroup, the total healthcare cost for patients treated with T-DXd was €204,262.69, compared with €71,596.21 with standard therapy. T-DXd provided 1.33 QALYs (2.46 life years), while standard therapy provided 1.08 QALYs (1.99 life years). The ICUR for T-DXd compared with SOC was €541,758.59/QALY. The estimated 5-year budget impact ranged from €72 million to €140 million for the overall population and €64 million to €124 million for the RH+ subgroup. CONCLUSIONS: Trastuzumab deruxtecan in HER2-low advanced or metastatic breast cancer shows limited cost effectiveness and represents a significant budgetary challenge for the Spanish National Health System, particularly in RH+ patients.