HER2-Targeted Antibody-Drug Conjugate Toxicities in Breast Cancer

Area of Science:

• Oncology
• Pharmacology

Background:

• HER2-targeted antibody-drug conjugates (ADCs) represent a significant advancement in breast cancer treatment.
• Two approved ADCs, trastuzumab deruxtecan and trastuzumab emtansine, are widely used, with over 60 additional candidates in development.

Purpose of the Study:

• To review current data on the toxicities associated with HER2-targeted ADCs in breast cancer.
• To highlight common and serious adverse events, as well as dose-limiting toxicities.

Main Methods:

• A narrative review of existing clinical trial data.
• Focus on adverse events reported for trastuzumab emtansine and trastuzumab deruxtecan.

Main Results:

• Trastuzumab emtansine is associated with epistaxis, fatigue, headache, nausea, and pyrexia.
• Trastuzumab deruxtecan commonly causes alopecia, cytopenias, decreased appetite, fatigue, and gastrointestinal issues.
• Adverse events occur even at suboptimal doses, limiting dose escalation for maximal efficacy.

Conclusions:

• Despite clinical benefits, HER2-targeted ADCs cause diverse systemic and organ-specific toxicities.
• These adverse events, including dose-limiting toxicities, pose barriers to maximizing therapeutic efficacy.
• Further research is needed to mitigate ADC-related toxicities in breast cancer patients.