OBJECTIVES: To evaluate the cost-effectiveness of trastuzumab deruxtecan compared to chemotherapy of physician’s choice for patients with human epidermal growth factor receptor 2 positive (HER2+) locally advanced or metastatic gastric or gastroesophageal junction cancer previously treated with at least two lines of therapy.

METHODS: A three-state partitioned survival model was developed to estimate the cost-effectiveness of trastuzumab deruxtecan (T-DXd) compared to chemotherapy treatment of physician’s choice (TPC). Modeled patients were administered T-DXd every 3 weeks or TPC every 2 weeks indefinitely or until disease progression. Transition parameters for the progression-free, post-progression, and death health states were principally derived from the DESTINY-Gastric01 phase II randomized clinical trial. Drug costs were extracted from CMS Average Sales Price (ASP), and administrative, adverse event, and end-of-life therapy costs derived from published literature, measured in 2023 US Dollars. Health state utilities and disutilities used to establish quality-adjusted life years (QALYs), including from treatment response, disease progression, and adverse events were sourced from published literature. Both probabilistic and deterministic sensitivity analyses were conducted 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 $363,994, compared to $80,261 for physician’s choice chemotherapy. Total QALYs for trastuzumab deruxtecan were 0.905, compared to 0.558 for chemotherapy. The base-case ICER was $819,477/QALY. Probabilistic sensitivity analysis indicated that trastuzumab deruxtecan had a 0% 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 $615, compared to the current drug cost (ASP + 6%) of $2,717.

CONCLUSIONS: Despite the higher efficacy of trastuzumab deruxtecan in patients with HER2+ advanced gastric cancer, our model highlights serious concerns regarding its cost-effectiveness.