OBJECTIVES: To assess the cost-effectiveness of trastuzumab deruxtecan compared to trastuzumab emtansine as second-line therapy for patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer.

METHODS: A three-state partitioned survival model was developed to estimate the cost-effectiveness of trastuzumab deruxtecan compared to trastuzumab emtansine. For both treatments, modeled patients were administered treatment intravenously every three weeks indefinitely or until disease progression. Transition parameters were principally derived from the DESTINY-Breast03 phase III randomized clinical trial and SEER data. Costs include drug costs extracted from CMS Average Sales Price and administrative, adverse event, and third-line therapy costs derived from published literature, measured in 2022 US Dollars. Quality-adjusted life years (QALYs), including from treatment, remissions and adverse events, were sourced from published literature. We conducted both probabilistic sensitivity analysis and comprehensive scenario analysis to test model assumptions and robustness. We utilized a five-year time horizon and a health system payers' perspective.

RESULTS: In our base-case analysis, total costs for trastuzumab deruxtecan were $668,204, compared to $479,055 for trastuzumab emtansine. Total QALYs for trastuzumab deruxtecan were 2.71, compared to 1.84 for trastuzumab emtansine. The base-case ICER was $217,397/QALY. Probabilistic sensitivity analysis indicated that trastuzumab deruxtecan had a 25.2% probability of being cost-effective at a $150,000 per QALY willingness-to-pay (WTP) threshold. Using this WTP threshold, the value-based price of trastuzumab deruxtecan per 100-mg vial to be cost-effective was $2,349, compared to the current drug cost (ASP + 6%) of $2,609.

CONCLUSIONS: Despite the higher efficacy of trastuzumab deruxtecan in patients with HER2+ metastatic breast cancer, our findings raise concern regarding its cost-effectiveness.