Trastuzumab deruxtecan versus chemotherapy for patients with HER2-low advanced breast cancer: A US-based cost-effectiveness analysis

Background: In recent years, the rise of antibody–drug conjugates (ADCs) has changed the treatment paradigm for patients with HER2-low advanced breast cancer (ABC). DESTINY-Breast04 (NCT03734029) has demonstrated the antitumor activity of trastuzumab deruxtecan (T-DXd). However, the balance between the efficacy and cost of T-DXd remains undefined. Consequently, there is a great need to assess the cost-effectiveness of T-DXd for patients with HER2-low ABC when compared with chemotherapy. Methods: A Markov decision-analytic model with a time horizon of 15 years was employed to estimate the costs and clinical efficacy of trials with the administration of T-DXd in contrast to chemotherapy alone as a later-line therapy in a group of patients with hormone receptor-positive (HR+) or negative (HR-) HER2-low ABC. The US payer perspective was taken into account when factors such as medical lifetime expenditure, incremental cost-effectiveness ratios (ICERs), and quality-adjusted life years (QALYs) were calculated. Sensitivity analyses were used to determine the model’s stability. A subgroup analysis was also conducted on the HR+/HER2-low cohort. Results: T-DXd was associated with an improvement of 0.543, 0.558, and 0.789 QALYs when compared with treatment with chemotherapy for overall, HR+, and HR- HER2-low patients, respectively. However, incorporating T-DXd into later-line therapy led to increased costs ($161,406, $177,907, and $155,757), which causes the ICER for T-DXd to be $296,873, $318,944, and $197,355 per QALY. The cost of T-DXd and the patient’s weight were the most influential factors for ICER. T-DXd being the dominant strategy is about 1.5%, 0.5%, and 28.0% in overall, HR+, and HR- HER2-low ABC patients, respectively. In addition, the T-DXd regimen was not cost-effective in all subgroups. Conclusion: Compared with chemotherapy, T-DXd was not cost-effective for patients with HER2-low ABC in the United States. However, it can provide more health benefits to patients with HR+/HER2-low ABC.