Interstitial lung disease risk and outcomes across HER2-targeted therapies commonly used in breast cancer: Analysis of real-world FAERS data.

e24206 Background: Anti-HER2 therapies, including the monoclonal antibody Trastuzumab and antibody-drug conjugates (ADCs) TDM-1 and TDX-d, have transformed treatment for HER2-positive breast cancers. While effective, all these agents carry the risk of interstitial lung disease (ILD), a serious adverse event with newer ADCs, particularly TDX-d, may pose a higher ILD risk. Assessing the real-world comparative risk is vital for clinical decision-making. This study uses the FAERS database to compare the reporting risk of ILD among Trastuzumab, TDM-1, and TDX-d. Methods: We conducted a retrospective FAERS data review to assess the ILD risk of Trastuzumab, TDM-1, and TDX-d from 2020 to 2026. The chi-square test was used to compare categorical variables across drugs and age groups ( < 65 vs ≥65 years). Results: Among 47,068 total cases (Trastuzumab n = 30,067; TDM-1 n = 5,805; TDX-d n = 11,196), TDX-d demonstrated the highest risk of ILD toxicity rate at 13.1% compared to 2.7 % for TDM-1 and 1.9 % for Trastuzumab (χ² = 2339.3, p0.001). Age-stratified analysis revealed persistence of the pattern of ILD toxicity rate across the three treatment groups, for < 65 and ≥65 years. For < 65 years, TDX-d demonstrated the highest risk of ILD toxicity rate at 11.7% compared to 2.04 % for TDM-1 and 1.2 % for tratsuzumab (χ² = 1021.6, p0.001). For ≥65 years, TDX-d demonstrated the highest risk of ILD toxicity rate at 15.3% compared to 4.6% for TDM-1 and 3.4% for Trastuzumab (χ² = 347.4, p0.001). Older patients ≥65 years have a significantly higher risk of ILD compared with patients < 65 years across all three treatment groups (TDX-d: 11.7% vs 15.3%, p000.2; TDM-1: 2.04% vs 4.6%, p0.001; Trastuzumab: 1.27% vs 3.46%, p0.001). Among patients who developed ILD, deaths and hospitalization were assessed across the drugs. TDX-d demonstrated the highest death rate of 4.04%, followed by TDM-1 with 0.49%, and Trastuzumab with 0.34% (χ² = 941.4, p0.001). The hospitalization rate was also noted to be higher for TDX-d (5.18%) compared to TDM-1 (1.06%) and Trastuzumab (0.81%), p0.001. Conclusions: The findings in this study highlight the trends of ILD among various HER2-targeted therapies. TDX-d demonstrated disproportionately lower hospitalization rates relative to the mortality burden compared to TDM-1 and Trastuzumab. This underscores the need for enhanced monitoring, early detection strategies, and lower thresholds for hospitalization in patients receiving TDX-d.