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

Abstract

BACKGROUND: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor–positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. METHODS AND RESULTS: Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4/6 inhibitor were included in the analysis. CVAEs identified from International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes included hypertension, atrial fibrillation(AF)/atrial flutter (AFL), heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine–Gray model) was used to determine the association between CDK4/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all-cause death was studied using Cox proportional hazard models. Propensity-weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person-years). CVAEs were slightly higher in patients who received CKD4/6 inhibitors compared with anthracyclines (P=0.063), with higher death rate associated with the development of AF/AFL or cardiomyopathy/heart failure in the CDK4/6 group. The development of cardiomyopathy/heart failure and AF/AFL was associated with increased allcause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98–8.05]; and 5.88 [95% CI, 3.56–9.73], respectively). CONCLUSIONS: CVAEs may be more common with CDK4/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.