Cardiac toxicity of HER-2 targeting antibody-drug conjugates: overview and clinical implications

Area of Science:

• Oncology
• Cardiology
• Pharmacology

Background:

• Antibody-drug conjugates (ADCs) offer targeted cancer therapy by combining monoclonal antibodies with chemotherapy.
• HER-2 is vital for cardiac development and physiology, making HER-2 targeting ADCs a concern for cardiotoxicity.
• Trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) are associated with cardiac toxicity, though often not clinically significant.

Purpose of the Study:

• To comprehensively review and characterize the cardiac toxicity profile of HER-2 targeting ADCs.
• To enhance clinical understanding of HER-2 ADC-related cardiotoxicity.
• To guide better recognition, monitoring, and management of cardiac adverse events associated with HER-2 ADCs.

Main Methods:

• Literature review of studies on HER-2 ADCs and cardiac side effects.
• Analysis of reported cardiac toxicity associated with T-DM1 and T-DXd.
• Synthesis of information on the role of HER-2 in cardiac function and its implications for ADC therapy.

Main Results:

• HER-2 ADCs, including T-DM1 and T-DXd, are consistently linked to cardiac toxicity.
• While cardiac adverse events are rarely clinically relevant, they require careful monitoring.
• Baseline cardiac evaluation and ongoing monitoring are crucial for patients receiving HER-2 ADCs.

Conclusions:

• HER-2 ADCs necessitate vigilant cardiac monitoring due to potential cardiotoxicity.
• Improved understanding of cardiac adverse events will optimize patient management.
• Early detection and management strategies are essential for safe and effective use of HER-2 ADCs.