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.