Cost and Cost-Effectiveness of Treating Human Epidermal Growth Factor Receptor 2–Low Metastatic Breast Cancer

PURPOSE Creating value-aligned treatment pathways in breast cancer requires understanding the cost and cost-effectiveness of new therapies. To address uncertainty in the optimal treatment sequence, we developed a decision model to assess the cost-effectiveness of various treatment sequences for patients with human epidermal growth factor receptor 2 (HER2)–low metastatic breast cancer who are eligible for trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) under current US Food and Drug Administration labeling. METHODS We derived disease progression and therapy data from the Destiny-Breast04 trial and sourced cost and quality-of-life data from the published literature. Our simulation modeled 57-year-old women with HER2-low, endocrine refractory, and triple-negative metastatic breast cancer eligible for third-line treatment. We evaluated four sequences: chemotherapy (chemo) → chemo, T-DXd → chemo, chemo → T-DXd, and T-DXd → SG. Outcomes included quality-adjusted life years (QALYs), total lifetime costs (2020 US dollars [USD], 3% annual discount), and incremental cost-effectiveness ratios. Sequences that cost <$150,000 USD to gain an additional QALY were considered cost effective. RESULTS Chemo → chemo has the lowest cost at $176,000 (USD) per patient and yields 0.82 QALYs. T-DXd → chemo costs $282,000 (USD) and yields 1.08 QALYs, with an incremental cost-effectiveness ratio of $408,000 (USD) per QALY gained. T-DXd → SG costs $304,000 (USD) and yields 1.09 QALYs, with an incremental cost-effectiveness ratio of $2,200,000 (USD) per QALY gained. Drug cost drives the cost differences between each strategy. For T-DXd → chemo to be cost effective at the $150,000 (USD) per QALY threshold, we estimate that a 41% price reduction for T-DXd is needed. CONCLUSION At its current price, T-DXd is not cost effective for HER2-low metastatic breast cancer. Price reductions can make this drug cost effective. Optimal value-based sequencing in this patient population uses a single antibody-drug conjugate rather than back-to-back conjugates.