Economic Evaluation of Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer in the United States

Purpose: Recently, the DESTINY-Breast04 trial revealed that significant benefits in both overall survival (OS) and progression-free survival (PFS) in patients with HER2-low advanced or metastatic breast cancer treated with trastuzumab deruxtecan (T-DXd) compared with chemotherapy. The current study assessed the cost-effectiveness of T-DXd from the perspective of the United States payer.Methods: We developed a partitioned survival model to project the disease course of breast cancer. The OS and PFS data were derived from the DESTINY-Breast04 trial. We extrapolate the survival data beyond the follow-up time to assess the long-term survival prognosis. Direct medical costs and utility data were collected. The incremental cost-utility ratio (ICUR) was the primary outcome that evaluated the cost-effectiveness of a therapy regimen. One-way sensitivity and probabilistic sensitivity analysis were implemented to explore the uncertainty of outputs.Results: In the base-case, the ICUR of T-DXd versus chemotherapy is $346,571.8/QALY and $337,789.4/QALY for all patients group and hormone-receptor-positive (HR+) subgroup, respectively. One-way sensitivity analyses revealed that the hazard ratio of OS, the unit cost of T-DXd, and body weight had a relatively large impact on the base-case result. Probabilistic sensitivity analyses showed that the likelihood that T-DXd was cost-effective is 14.5% and 12.6% for all patients group and HR+ subgroup, respectively.Conclusion: The cost-effectiveness analysis suggested that, at current price, trastuzumab deruxtecan is unlikely to be a preferred option for patients with HER2-low breast cancer at a threshold of $150,000/QALY from a US payer perspective.