Profiling the Cardiovascular Toxicities of CDK4/6 Inhibitors: A Real-World Pharmacovigilance Study

Area of Science:

• Oncology
• Cardiology
• Pharmacovigilance

Background:

• Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive, HER2-negative breast cancer.
• The cardiovascular safety profile of CDK4/6 inhibitors requires further elucidation.
• Understanding cardiac events associated with these targeted therapies is crucial for patient management.

Purpose of the Study:

• To systematically profile cardiac adverse events linked to CDK4/6 inhibitors.
• To identify specific cardiovascular toxicities associated with palbociclib, ribociclib, and abemaciclib.
• To assess the safety signals for cardiovascular events using established pharmacovigilance methodologies.

Main Methods:

• Analysis of FDA Adverse Event Reporting System (FAERS) data from Q1 2015 to Q1 2024.
• Inclusion of reports where palbociclib, ribociclib, or abemaciclib were the primary suspect drugs.
• Application of signal detection algorithms: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC).

Main Results:

• A total of 69,139 reports were reviewed, with 2065 documenting cardiac adverse events.
• Hypertension and cardiac failure were the most frequently reported cardiovascular toxicities.
• A confirmed safety signal for ribociclib and QT prolongation was re-identified (PRR 8.43, ROR 8.65, IC025 2.86).

Conclusions:

• CDK4/6 inhibitor use is associated with significant cardiovascular adverse events, including heart failure and hypertension.
• The findings highlight the need for vigilant cardiac monitoring in patients receiving CDK4/6 inhibitors.
• Further investigation into the underlying mechanisms and risk factors for CDK4/6 inhibitor-associated cardiotoxicity is warranted.