OBJECTIVES: Pre-treated patients with inoperable/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) have limited treatment options with varied safety profiles. The economic burden of severe adverse event (AE) management in this population is unclear. We aimed to estimate the total costs of managing Grade ≥3 AEs (G3AEs) following treatment with datopotamab deruxtecan (Dato-DXd), sacituzumab govitecan (SG) and investigator-choice of chemotherapy (ICC) utilizing safety data from clinical trials.

METHODS: Treatment-related AE data were extracted from Phase III trial reports evaluating Dato-DXd (TROPION-Breast01), SG (TROPiCS-02) and the respective ICC arms. An incidence cut-off of ≥10% was applied for all grade AEs to determine inclusion of G3AEs. AEs of special interest for Dato-DXd were also included. Given the severity of AEs, it was assumed all patients are treated in hospital; inpatient unit costs were sourced from health ministry public databases for Italy and Spain and the Healthcare Cost and Utilization Project data for the US. All costs were inflated to 2024.

RESULTS: Total costs were highest in the US, followed by Spain and Italy for all treatments. Within-study comparisons versus ICC demonstrated that Dato-DXd was associated with substantially lower costs (on average 72% lower than the respective ICC) whereas SG was associated with higher total costs (on average 28% higher than the respective ICC). To a large extent results were driven by the large reduction in neutropenia incidence with Dato-DXd, but scenarios excluding neutropenia showed at least a 27% reduction in G3AE management costs for Dato-DXd vs ICC.

CONCLUSIONS: Dato-DXd has an acceptable safety profile in HR+/HER2- BC and is associated with lower costs of managing G3AEs in Italy, Spain and the US compared with SG and ICC. The results should be interpreted with caution due to cross trial and country differences in AE management.