Trastuzumab deruxtecan versus trastuzumab emtansine for human epidermal growth factor receptor 2 positive metastatic breast cancer: cost-effectiveness analysis from Iranian experience

Background: This study evaluates the cost-effectiveness of trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) as second-line treatments for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in Iran.
Methods: A partitioned survival model was constructed using time-to-event data from the DESTINY-Breast03 trial to assess the cost-effectiveness of T-DXd versus T-DM1 from a societal perspective over a lifetime horizon. Cost and utility inputs were sourced from published literature and official Iranian data. Key outcomes included total costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). A willingness-to-pay (WTP) threshold of $2,413 per QALY was applied. Uncertainty was explored through one-way and probabilistic sensitivity analyses (PSA).
Results: In the base-case analysis, T-DXd produced 3.59 QALYs at a cost of $261,315, while T-DM1 yielded 1.89 QALYs at $258,039. The resulting ICER for T-DXd was $1,927 per QALY—below Iran’s WTP threshold. The unit cost of T-DXd was identified as the most influential variable in one-way sensitivity analysis. PSA showed that T-DXd had a 52% probability of being cost-effective.
Conclusion: T-DXd is a cost-effective alternative to T-DM1 as a second-line therapy for HER2-positive MBC in Iran. Its favorable clinical outcomes and an ICER below the national WTP threshold support its inclusion in treatment protocols for this patient group.