The phase two DESTINY-Gastric-01 trial demonstrated that trastuzumab deruxtecan (T-DXd) improved overall survival in Asian patients with human epidermal growth factor receptor 2 (HER2)-positive, advanced gastric or gastroesophageal adenocarcinoma that had progressed following two or more treatments, compared with chemotherapy (irinotecan or paclitaxel monotherapy). Considering the high cost of T-DXd, we assessed the cost-effectiveness of T-DXd versus chemotherapy from the Singapore healthcare system’s perspective.

A partitioned survival model with three health states (progression-free, progressed disease and death) was developed, with a five-year time horizon. Survival curves from DESTINY-Gastric-01 were extrapolated beyond the trial duration using parametric functions. Health state utilities were obtained from published literature and direct costs were sourced from public healthcare institutions in Singapore. Utility decrements for adverse events such as interstitial lung disease was incorporated into the model for the differences in safety profiles. A discount rate of three percent was applied to costs and outcomes. One-way deterministic sensitivity analyses (OWSA) and scenario analyses were conducted to assess parameter and model uncertainties.

Treatment with T-Dxd, compared to chemotherapy, had a high base case incremental cost-effectiveness ratio (ICER) of over SGD450,000 (USD334,900) per quality-adjusted life-year gained. The cost of T-DXd greatly influenced the results according to OWSA. Seventy-three percent of the total costs accrued in the T-DXd arm was due to the cost of the drug, compared to seven percent in the chemotherapy arm. The ICER was also sensitive to the assumptions around extrapolation of the survival curves, but when tested across all scenario analyses, the results remained unfavorable.

At the current cost, T-DXd does not represent good value compared to chemotherapy for previously treated HER2-positive gastric cancer in Singapore. The findings from our cost-effectiveness analysis, alongside other considerations, will be useful to inform policy makers on funding decisions.