A cost-effectiveness analysis of trastuzumab deruxtecan for HER2-low metastatic breast cancer: applying a Saudi economic evaluation guideline

Background This study evaluated the cost-effectiveness of trastuzumab deruxtecan (T-DXd) versus chemotherapy for HER2-low metastatic breast cancer. It also assessed the practical application of the authors’ previously developed Saudi economic evaluation guideline, highlighting key challenges and potential solutions. Methods A state-transition Markov model with a one-month cycle and a 10-year time horizon was used. Transition probabilities were derived from the DESTINY-Breast04 trial, and cost data were obtained from institutional sources. Outcomes included life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), with costs and health outcomes discounted at 3% annually. Sensitivity analyses were conducted to assess the impact of uncertainty on key parameters. Results T-DXd yielded 0.48 additional QALYs and 0.69 LYs at an additional cost of SAR 214,257 (US$57,135). The ICER was SAR 448,868 per QALY gained (US$119,698/QALY) and SAR 310,517 per LY gained (US$82,804/LY), both exceeding the Saudi willingness-to-pay (WTP) threshold of SAR 120,000 per QALY gained. T-DXd acquisition cost was the most influential factor. With an 80% price reduction and a WTP threshold of SAR 260,000 per QALY gained, the probability of cost-effectiveness increased to approximately 30%. Conclusions While clinically effective, T-DXd was not cost-effective at current pricing in Saudi Arabia. Application of the country-specific economic evaluation guideline illustrated its practical use and highlighted areas for further development of local health economic research.