Cardiovascular Safety of Next-Generation Antibody-Drug Conjugates in HER2-Low and Triple-Negative Breast Cancer: A...

Area of Science:

• Oncology
• Cardiology
• Pharmacology

Background:

• The HER2-low phenotype has expanded eligibility for HER2-targeted antibody-drug conjugates (ADCs).
• Trastuzumab deruxtecan (T-DXd) is a novel ADC targeting HER2, but it presents a unique cardiotoxicity profile.
• Previous ADCs had different cardiac safety profiles.

Purpose of the Study:

• To review the cardiotoxicity associated with Trastuzumab deruxtecan (T-DXd).
• To compare the cardiac safety signals of T-DXd with TROP2-directed ADCs.
• To propose a cardiac monitoring algorithm for next-generation ADCs.

Main Methods:

• Narrative review of recent literature.
• Analysis of pharmacovigilance reports.
• Review of real-world data on cardiac events.

Main Results:

• T-DXd is associated with a notable incidence of left ventricular ejection fraction (LVEF) decline.
• The cardiotoxicity of T-DXd is higher than earlier-generation ADCs.
• TROP2-directed ADCs show negligible cardiac signals.

Conclusions:

• Serious cardiac events with T-DXd have a high fatality rate.
• A risk-stratified cardiac monitoring algorithm using high-sensitivity troponin and global longitudinal strain is proposed.
• This algorithm aims to improve patient safety with next-generation ADCs.