Treatment-Related Cardiotoxicity in Non-Small Cell Lung Cancer: A Population-Based Analysis for Risk Stratification.

[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.