Adverse Cardiovascular Events Associated With Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Metastatic...

Area of Science:

• Oncology
• Cardiology
• Pharmacology

Background:

• Cyclin-dependent kinase (CDK) 4 and 6 inhibitors improve survival in metastatic breast cancer.
• Limited data exist on the cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors.

Purpose of the Study:

• To investigate the epidemiology of CVAEs in patients treated with CDK4/6 inhibitors.
• To assess the association between CDK4/6 inhibitor therapy and incident CVAEs.
• To determine the impact of CVAEs on all-cause mortality.

Main Methods:

• Retrospective analysis of adult patients without prior cardiovascular disease who received CDK4/6 inhibitors using the OneFlorida Data Trust.
• Identification of CVAEs using ICD-9/10 codes.
• Competing risk analysis (Fine-Gray model) and Cox proportional hazard models were employed.
• Propensity-weight analyses compared CDK4/6 inhibitor patients to anthracycline-treated patients.

Main Results:

• 1376 patients treated with CDK4/6 inhibitors were analyzed.
• CVAEs occurred in 24% of patients (35.9 per 100 person-years).
• CVAEs were slightly higher in the CDK4/6 inhibitor group compared to anthracyclines (P=0.063).
• Development of atrial fibrillation/flutter (AF/AFL) or cardiomyopathy/heart failure was associated with increased all-cause death (HRs 5.88 and 4.89, respectively).

Conclusions:

• CVAEs may be more frequent with CDK4/6 inhibitors than previously recognized.
• Increased mortality is associated with AF/AFL or heart failure in patients receiving CDK4/6 inhibitors.
• Further research is needed to fully understand the cardiovascular risks of these novel anticancer agents.