HER2‐Targeted Antibody‐Drug Conjugate Toxicities in Breast Cancer

BACKGROUND: HER2-targeted antibody-drug conjugates (ADCs) have dramatically advanced breast cancer outcomes. Two HER2-targeted ADCs, trastuzumab deruxtecan and trastuzumab emtansine, are currently approved for use in breast cancer, with > 60 other candidates under ongoing investigation. METHODS: In this report, we provide a narrative review of existing data underlying the current understanding of HER2-targeted ADC toxicities in breast cancer, highlighting both common and serious adverse events. RESULTS: When used as an adjuvant or neoadjuvant, first- or second-line agent, alone or in combination with another agent, trastuzumab emtansine has been commonly associated with epistaxis, fatigue, headache, nausea, and pyrexia across several clinical trials. Comparatively, trastuzumab deruxtecan has been commonly associated with alopecia, cytopenias, decreased appetite, fatigue, and gastrointestinal adverse effects. CONCLUSION: Despite the demonstrated clinical benefits in breast cancer, diverse systemic and organ-specific adverse events, including dose-limiting toxicities, have been reported even at suboptimal therapeutic doses and pose significant barriers to pursuing dose escalations for maximizing therapeutic efficacy.