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Updated: Mar 27, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Treatment-Related Cardiotoxicity in Non-Small Cell Lung Cancer: A Population-Based Analysis for Risk Stratification
You Mo1,2, Duncan Wei1, Xinyi Liang2
1Department of Cardiovascular Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Background:
The cardiovascular toxicity profiles of different treatment regimens for non-small cell lung cancer (NSCLC) remain unclear.
Aims:
To investigate the associations between NSCLC therapies and arrhythmias, heart failure, pericardial diseases, cardiomyopathy, and coronary artery diseases.
Design:
An observational cohort study.
Methods:
The cardiovascular toxicity risk of anticancer therapies in NSCLC patients was evaluated in a pharmacovigilance study. Exposures included targeted therapy (TARGET), chemotherapy (CHEMO), radiotherapy (RT), immune checkpoint blockade (ICB), and combination therapies.
Results:
This observational study (n = 5,242) revealed that ICB-RT combinations had superior cardiovascular safety to other regimens. Targeted therapies showed elevated heart failure risk (TARGET vs ICB: 1.32 (95% CI: 1.13-1.53), P < 0.001). Chemotherapy increased coronary artery disease risk (CHEMO vs ICB: 1.28 (95% CI: 1.03-1.60), P = 0.029). ICB showed higher pericardial disease risks (ICB vs CHEMO: 5.88 (95% CI: 4.00-8.33), P < 0.001). Platinum-taxane combinations had 2.14 times higher coronary risk than antimetabolites. Reactive oxygen species 1 (ROS1)/neurotrophic receptor tyrosine kinase (NTRK)/mesenchymal-epithelial transition (MET) inhibitors showed greater heart failure risk (OR = 2.14, 95% CI: 1.41-3.28, P < 0.001) vs EGFR inhibitors. Anti-PD-L1 (OR = 0.68, 95% CI 0.51-0.91, P = 0.009) and anti-CTLA-4 (OR = 0.57, 95% CI: 0.37-0.86, P = 0.008) demonstrated lower pericardial risk versus anti-PD-1.
Conclusions:
These findings support the use of ICB plus RT in patients with high cardiovascular risk, while caution is advised with ROS1/NTRK/MET inhibitors and platinum-taxane chemotherapy. Anti-PD-L1 and anti-CTLA-4 may be preferred over anti-PD-1 in patients at risk for pericardial toxicity.
Insights
Immune checkpoint blockade plus radiation therapy (ICB-RT) shows superior cardiovascular safety for non-small cell lung cancer (NSCLC) patients. Targeted therapies and chemotherapy increase risks for heart failure and coronary artery disease, respectively.
Area of Science:
- Oncology
- Cardiology
- Pharmacovigilance
Background:
- Cardiovascular toxicity of non-small cell lung cancer (NSCLC) treatments is not fully understood.
- Different anticancer therapies may pose varying risks to cardiac health.
Purpose of the Study:
- To evaluate the association between NSCLC therapies and major cardiovascular adverse events.
- To compare the cardiovascular safety profiles of targeted therapy, chemotherapy, radiotherapy, immune checkpoint blockade, and combination regimens.
Main Methods:
- Observational cohort study including 5,242 NSCLC patients.
- Pharmacovigilance analysis of cardiovascular toxicity risks associated with various anticancer therapies.
- Comparison of risks for arrhythmias, heart failure, pericardial diseases, cardiomyopathy, and coronary artery diseases across treatment groups.
Main Results:
- Immune checkpoint blockade plus radiotherapy (ICB-RT) demonstrated the best cardiovascular safety profile.
- Targeted therapies (TARGET) were linked to increased heart failure risk (1.32 times higher than ICB).
- Chemotherapy (CHEMO) increased coronary artery disease risk (1.28 times higher than ICB), and platinum-taxane combinations showed 2.14 times higher coronary risk than antimetabolites.
- Immune checkpoint blockade (ICB) was associated with higher pericardial disease risk (5.88 times higher than CHEMO).
- ROS1/NTRK/MET inhibitors showed greater heart failure risk (OR=2.14) compared to EGFR inhibitors.
- Anti-PD-L1 and anti-CTLA-4 therapies were associated with lower pericardial disease risk compared to anti-PD-1.
Conclusions:
- ICB plus RT is a favorable option for NSCLC patients with high cardiovascular risk.
- Caution is advised when using ROS1/NTRK/MET inhibitors and platinum-taxane chemotherapy due to increased heart failure and coronary risk.
- Anti-PD-L1 and anti-CTLA-4 may be preferred over anti-PD-1 in patients susceptible to pericardial toxicity.
