Comparison of cardiovascular outcomes among solid tumor ADCs: A tumor-agnostic observational study.

Abstract

e15208 Background: Antibody-drug conjugates (ADCs) combine monoclonal antibodies with cytotoxic payloads to selectively deliver chemotherapy to tumor cells. Despite their targeted design, cardiovascular toxicity remains a significant concern. Cardiac adverse events include heart failure, left ventricular dysfunction, arrhythmias, and QT prolongation. Our study aims to assess the comparative cardiovascular toxicity profile of seven FDA-approved ADCs. Methods: We utilized data from the Global Collaborative Network-TriNetX to assess cardiovascular outcomes associated with seven ADCs: trastuzumab deruxtecan, sacituzumab govitecan, enfortumab vedotin, ado-trastuzumab emtansine, tisotumab vedotin, mirvetuximab soravtansine, and datopotamab deruxtecan. Using ICD-10 codes, we evaluated cardiomyopathy, congestive heart failure (CHF), heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), arrhythmias, myocarditis, and mean QT interval prolongation. Incidence was calculated as the proportion of patients experiencing each outcome among all patients exposed to each ADC. Results: Ado-trastuzumab emtansine demonstrated the highest cardiomyopathy incidence at 7.204% (n = 287, N = 3,984), followed by enfortumab vedotin at 6.36% (n = 249, N = 3,915) and sacituzumab govitecan at 5.338% (n = 170, N = 3,185). Trastuzumab deruxtecan showed 2.541% (n = 157, N = 6,179). For CHF, enfortumab vedotin and sacituzumab govitecan showed the highest rates at 2.406% and 2.231%, respectively. HFrEF occurred most frequently with enfortumab vedotin (3.184%) and ado-trastuzumab emtansine (3.122%). Arrhythmias were most common with enfortumab vedotin (7.628%) and sacituzumab govitecan (6.753%). Myocarditis was rare, with enfortumab vedotin reporting 0.464%. Tisotumab vedotin demonstrated the longest mean QT interval at 450ms (Std Dev 51ms), followed by mirvetuximab soravtansine at 435ms and enfortumab vedotin at 430ms. Conclusions: Our study demonstrates significant variability in cardiovascular toxicity among ADCs. Ado-trastuzumab emtansine, enfortumab vedotin, and sacituzumab govitecan showed the highest cardiomyopathy and heart failure rates, while trastuzumab deruxtecan demonstrated a favorable profile. These findings highlight the importance of cardiovascular risk stratification and monitoring in patients receiving ADC therapy. Given this is a retrospective observational study, prospective trials with standardized cardiovascular monitoring are warranted.