Key result
CDK4/6 inhibitors show similar cardiovascular event rates compared to anthracyclines.
Why the study?
There are few data regarding the epidemiology of cardiovascular adverse events associated with cyclin-dependent kinase 4 and 6 inhibitors in patients with metastatic breast cancer.
Does CDK4/6 inhibitor therapy increase the risk of cardiovascular adverse events and subsequent mortality compared with anthracyclines in female patients with breast cancer without prior cardiovascular disease?
Cohort (n=2,591)
Yes
Does CDK4/6 inhibitor therapy increase the risk of cardiovascular adverse events and subsequent mortality compared with anthracyclines in female patients with breast cancer without prior cardiovascular disease?
Real-world data reveal that cardiovascular adverse events—particularly hypertension, heart failure, and atrial fibrillation/flutter—occur in nearly one-quarter of patients with metastatic breast cancer treated with CDK4/6 inhibitors and are associated with significantly higher mortality.
Answers are grounded in this paper and cite their sources.
Supports cardiovascular monitoring with CDK4/6 inhibitors; leaves open causality and need for confirmatory trials.
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 all‐cause 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.
No takes yet. Share an insight, caveat, or question.
Fradley et al. (2023) conducted a cohort in Breast cancer (metastatic breast cancer in the CDK4/6 inhibitor group) (n=2,591). CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) vs. Anthracyclines (without CDK4/6 or HER2 inhibitors) was evaluated on Incident cardiovascular adverse events (CVAEs: hypertension, atrial fibrillation/atrial flutter, heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease) within 12 months (p=0.063). CDK4/6 inhibitor therapy was associated with a 24% incidence of cardiovascular adverse events, which increased 3-year all-cause death.
Synapse has enriched 10 related papers. Consider them for comparative context: