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Cyclin-dependent kinase 4/6 inhibitors and cardiotoxic events in breast cancer: A pharmacovigilance study based on

Ting Li1,2,3, Miaomiao Zhang1,2,3, Tian Zhang1,2,3

  • 1Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China.

International Journal of Cancer
|November 14, 2024
PubMed

Insights

Ribociclib, a CDK4/6 inhibitor, shows significant cardiotoxicity, including QT prolongation. This study analyzed FDA data, revealing drug interactions and patient factors influencing cardiac events in breast cancer patients.

Area of Science:

  • Pharmacovigilance and Drug Safety
  • Oncology
  • Cardiology

Background:

  • Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are crucial in breast cancer therapy.
  • Recent trials indicate cardiotoxicity with ribociclib, a CDK4/6 inhibitor, specifically QT prolongation.
  • Inconsistent findings and underexplored influencing factors necessitate further investigation into CDK4/6 inhibitor cardiotoxicity.

Purpose of the Study:

  • To comprehensively examine cardiotoxic events associated with CDK4/6 inhibitors in breast cancer patients.
  • To identify specific cardiotoxic events and influencing factors, including drug interactions.
  • To compare the cardiotoxicity profiles of different CDK4/6 inhibitors.

Main Methods:

  • Utilized the FDA Adverse Event Reporting System database (Q1 2015 to Q1 2024).
  • Employed disproportionality analyses: Bayesian confidence propagation neural network, proportional reporting ratio, and reporting odds ratio.
  • Applied multivariable logistic regression and Bayesian network analyses to identify influencing factors and drug interactions.

Main Results:

  • Ribociclib demonstrated pronounced cardiotoxicity, significantly associated with torsade de pointes/QT prolongation and conduction defects.
  • Palbociclib showed positive signals for cardiotoxic events, including pulmonary edema, hypertension, myocardial infarction, and cardiac flutter.
  • Age, geographic location, and polypharmacy were identified as significant influencers of cardiotoxic events; specific drug interactions were highlighted.

Conclusions:

  • Significant variability exists in cardiotoxicity among CDK4/6 inhibitors, with ribociclib posing a higher risk.
  • First-time identification of palbociclib-associated cardiotoxic signals warrants further clinical attention.
  • Personalized treatment strategies considering patient factors and concomitant medications are essential for mitigating cardiotoxicity and enhancing patient safety.
Keywords:
cardiotoxic eventscyclin‐dependent kinase 4/6 inhibitorsdrug interactionsinfluencing factorspharmacovigilance

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