Safety management of anti TROP2 ADCs in patients with breast cancer

TROP2-directed antibody-drug conjugates (trophoblast antigen 2-directed ADCs) are becoming increasingly integrated into breast cancer treatment across multiple disease settings. Their expanding use makes a detailed understanding of agent-specific toxicities, underlying mechanisms and practical management strategies increasingly important.

Sacituzumab govitecan and datopotamab deruxtecan share TROP2 targeting and topoisomerase I inhibition but exhibit distinct safety profiles. Sacituzumab govitecan is mainly associated with neutropenia and diarrhoea, whereas datopotamab deruxtecan is characterized by stomatitis, ocular surface events and a low but clinically relevant risk of interstitial lung disease/pneumonitis. These differences reflect the integrated effects of payload, linker stability, drug-to-antibody ratio, tissue distribution and target-independent uptake. Recent clinical and real-world evidence has also refined preventive and supportive strategies, including granulocyte colony-stimulating factor (G-CSF) use, UGT1A1-informed risk assessment, steroid mouthwash, ophthalmological monitoring and early interstitial lung disease (ILD) recognition. Combination with immune checkpoint inhibitors appears to produce mainly overlapping rather than entirely new toxicity profiles.

Safety management of TROP2-directed ADCs should be agent-specific, proactive and increasingly individualized. Future approaches may incorporate pharmacogenomics, longitudinal monitoring, patient-reported outcomes and artificial intelligence to improve toxicity prediction, early detection and adaptive management.