Difference in Cost-Effectiveness of Trastuzumab Deruxtecan in First-Line Versus Later-Line Settings for HER2-Low...

Trastuzumab deruxtecan (T-DXd) is approved as first-line therapy for HER2-low metastatic breast cancer after endocrine therapy failure and as later-line therapy, but economic evidence comparing these two settings to inform sequencing decisions is lacking.

To compare the cost-effectiveness of T-DXd between first-line and later-line settings for HER2-low metastatic breast cancer from a Japanese healthcare payer perspective.

A partitioned survival model was developed using data from the DESTINY-Breast06 and DESTINY-Breast04 trials. The analysis adopted a Japanese healthcare payer perspective with a 30-year time horizon and 2% annual discounting for both costs and outcomes. Incremental cost-effectiveness ratios (ICERs) were compared against a willingness-to-pay threshold of 15 million JPY per quality-adjusted life-year (QALY). Deterministic, probabilistic, and scenario sensitivity analyses were conducted.

T-DXd yielded an ICER of 37.36 million JPY/QALY in the first-line setting and 63.29 million JPY/QALY in the later-line setting compared with physician's choice chemotherapy. Sensitivity analyses confirmed the robustness of these estimates, with first-line T-DXd consistently more favourable across scenarios.

T-DXd exceeded the willingness-to-pay threshold in both settings at current pricing, indicating it was not cost-effective. Although the first-line ICER was approximately 40% lower than the later-line ICER, achieving cost-effectiveness in the first-line setting requires a larger proportional price reduction because the comparator chemotherapy in that setting is less expensive. This first Japanese cost-effectiveness analysis directly comparing the two settings should inform pricing negotiations and highlight the need for predictive biomarkers of the T-DXd response.