Cost-effectiveness of datopotamab deruxtecan versus chemotherapy as a first-line treatment for patients with advanced triple-negative breast cancer

Background The phase III TROPION-Breast02 trial demonstrated improved progression-free and overall survival with datopotamab deruxtecan (Dato-DXd) versus chemotherapy in patients with previously untreated advanced triple-negative breast cancer who were ineligible for immunotherapy. This study evaluated the cost-effectiveness of Dato-DXd from the perspectives of the United States (U.S.) and Chinese healthcare systems. Methods A three-state partitioned survival model was developed using TROPION-Breast02 data, with a 10-year horizon and 21-day cycles. Costs and utilities were obtained from public databases and published literature. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life-year (QALY) gained. Willingness-to-pay thresholds were $150,000/QALY in the U.S. and $27,906/QALY in China. Sensitivity and scenario analyses assessed uncertainty and the robustness of the findings, and exploratory subgroup analyses were performed. Results Compared with chemotherapy, Dato-DXd increased costs by $565,572.29 and QALYs by 0.44 in the U.S., yielding an ICER of $1,287,001.65/QALY. In China, the corresponding increases were $39,052.50 and 0.42 QALYs, yielding an ICER of $92,640.82/QALY. Price reductions of approximately 62.43% in the U.S. and 28.83% in China were required to reach the respective cost-effectiveness thresholds. Progression-free survival utility and Dato-DXd price were the most influential parameters in one-way sensitivity analyses. In exploratory scenario analyses, limiting treatment duration to the reported median yielded cost-effective results in both countries. Assuming unchanged efficacy, a hypothetical reduction in the Dato-DXd dose from 6 to 4 mg/kg made it cost-effective in China but not in the U.S. Exploratory subgroup analyses yielded conclusions consistent with the base-case findings. Conclusion At the modeled prices and under the base-case assumptions, Dato-DXd was not cost-effective compared with chemotherapy in either country. Price reductions could improve its cost-effectiveness. Results were sensitive to assumptions about treatment duration. The potential economic benefits of reduced-dose or fixed-duration strategies depend on clinical confirmation of maintained efficacy and acceptable safety.