Cost-Effectiveness of Trastuzumab Deruxtecan in Patients with Unresectable or Metastatic HER2-Low Breast Cancer Who Have Received Prior Chemotherapy

In 2021, breast cancer affected 75,619 women in Denmark. Approximately 50% of breast cancers are considered human epidermal growth factor receptor 2 (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 6 months 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 DKK 621,325 in incremental costs compared to the treatment of physician’s choice. This resulted in an incremental cost-effectiveness ratio of DKK 795,181 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.