Racial and ethnic disparities in clinical outcomes of HER2-positive metastatic breast cancer treated with antibody-drug conjugates: A TriNetX real-world evidence study.

Abstract

1036 Background: HER2-positive breast cancer (HER2+ BC) is an aggressive BC subtype driven by overexpression of the human epidermal growth factor receptor 2 (HER2). Antibody drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1), both approved for metastatic HER2+ BC, have significantly improved survival in this population. However, racial and ethnic disparities in outcomes with ADCs remain unclear. Methods: De-identified data from TriNetX, a global federated health research network, were analyzed for patients with metastatic HER2+ BC receiving HER2-directed ADCs. Kaplan-Meier analysis assessed overall survival. Statistical comparisons of survival rates between groups were made using log-rank tests. Propensity matching was used to adjust for age, comorbidities and lines of treatment. Two-sided P ≤0.05 was used to determine statistical significance. Results: A total 7,462 patients were included in this analysis. The median age was 56.2 years (range: 43-69), 68% were Non-Hispanic White (NHW), 17% Black, 5% Asian, and 10% Hispanic. 4,774 pts received TDM-1, 1,547 received T-DXd, and 1,141 received both. 37.6% patients treated with TDM-1 and 64.3% treated with T-DXd received >2 lines of prior therapy. Overall, the survival rate was 96% at 1 year, 89.3% at 3 years, and 83.7% at 5 years. At 3 years, the survival varied significantly by race: 90.3% in NHWs, 87.1% in Black, 92.9% in Asians, and 91.3% in Hispanics (p < 0.001). Similar differences extended to 5 years: NHW 85.0%, Black 80.9%, Asian 89.5%, Hispanic 86.7% (p<0.001) (Table). Among patients receiving T-DM1, the 3-year survival rate was 71.9%, compared to 45.7% in the T-DXd cohort (p<0.05). After adjusting for age and comorbidities, there was no difference in survival between patients who received T-DXd and TDM1 (not including who received both) (HR 2.55 (95% CI: 2.20–2.96; p = 0.75). Conclusions: Our study shows better outcomes with use of ADCs in heavily pretreated metastatic HER2-BC, with 83.7% of patients surviving beyond 5 years. However, significant racial disparities were observed, with Asian patients showing the highest survival while Black patients had the poorest survival which could be due to multi-level factors. Future studies are needed to understand the underlying mechanisms behind this racial disparity in outcomes with HER2-directed ADCs to inform strategies to improve patient outcomes. Survival rates and hazard ratios by race. Race 3-year survival probability (%) 5-year survival probability (%) Hazard Ratio NHW 89.60 83.96 1.00 Black 86.90 80.30 1.33 (95% CI: 1.26–1.40) Asian 92.26 88.92 0.69 (95% CI: 0.6–0.75) Hispanic 91.20 86.27 0.89 (95% CI: 0.83–0.95) NHW (Non-Hispanic White).