In 2021, breast cancer affected 75,619 women in Denmark. Approximately 50% of breast cancers are considered human epidermal growth factor receptor2 (HER2)-low. The DESTINY-Breast04 (DB-04) trial led to European Medicines Agency (EMA) approval of trastuzumab deruxtecan (T-DXd) as a treatment for patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6months of completing adjuvant chemotherapy. Moreover, the Danish Breast Cancer Group guidelines recently included T-DXd as a treatment for HER2-low metastatic breast cancer. This economic evaluation aims to estimate the cost-effectiveness of T-DXd for the approved EMA indication in Denmark. A three-state-progression-free, post-progression, and death-partitioned survival model was developed to estimate the cost-effectiveness of T-DXd versus treatment of physician's choice over a lifetime horizon following the Danish Medicines Council guidelines. Clinical data were gathered from the DB-04 trial, and cost and resource use data were sourced from the literature. Sensitivity and scenario analysis were conducted to explore uncertainty. T-DXd led to 0.78 incremental quality-adjusted life years (QALYs) gained and incurred DKK621,325 in incremental costs compared to the treatment of physician's choice. This resulted in an incremental cost-effectiveness ratio of DKK795,181 per QALY gained, which falls below the willingness-to-pay threshold. Sensitivity and scenario analyses showed the robustness of the deterministic result, with T-DXd remaining cost-effective. Our study demonstrates that T-DXd is a cost-effective treatment for patients with HER2-low unresectable or metastatic breast cancer who have received prior chemotherapy in Denmark.
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