Interstitial Lung Disease and Cardiotoxicity Associated with Trastuzumab Deruxtecan, Sacituzumab Govitecan, and Trastuzumab Emtansine: A Narrative Review.

Background and Objectives: Antibody-drug conjugates (ADCs) have become a major therapeutic platform in breast cancer and other solid tumors. Trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), and sacituzumab govitecan (SG) differ substantially in antibody target, linker, payload, drug-to-antibody ratio, and bystander effect, resulting in heterogeneous pulmonary and cardiac toxicity profiles. This narrative review critically compares interstitial lung disease (ILD)/pneumonitis and cardiotoxicity associated with these three agents, aiming to prevent inappropriate extrapolation of toxicity algorithms and to provide a practical, agent-specific framework for multidisciplinary care. Materials and Methods: A targeted narrative search of PubMed/MEDLINE, Google Scholar, ClinicalTrials.gov, regulatory product information, and oncology/cardio-oncology guidance was performed and updated on 24 August 2026. Priority was given to regulatory documents, pivotal trials, pooled safety analyses, real-world cohorts, systematic reviews, and multidisciplinary recommendations. Pharmacovigilance data and case reports were included only to characterize rare events. Results: T-DXd is associated with a clinically important ILD/pneumonitis risk (approximately 12-15% in pooled analyses), predominantly grade 1-2 but occasionally fatal, requiring proactive surveillance, immediate interruption for suspected disease, and grade-directed corticosteroid therapy. T-DM1 shows a low but established pneumonitis incidence of approximately 1%, with permanent discontinuation recommended upon diagnosis. SG-related pneumonitis is rare and incompletely defined, without a T-DXd-like surveillance mandate. Both T-DM1 and T-DXd retain trastuzumab-derived cardiac monitoring requirements; symptomatic heart failure remains uncommon, although protocol-defined LVEF declines appear more frequent with T-DXd. SG lacks an established cardiomyopathy signal. Conclusions: Cardiopulmonary toxicity of ADCs is agent-specific rather than a class effect. Monitoring intensity, diagnostic thresholds, and management pathways must be tailored to the individual drug, regimen, indication, dose, patient comorbidity, and prior therapy. Close collaboration among oncology, radiology, pulmonology, and cardio-oncology is essential to preserve both treatment efficacy and patient safety.