Immune checkpoint inhibitors in lung cancer: A retrospective cohort analysis of cardiovascular safety profiles.

Abstract

e20069 Background: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment, providing significant clinical benefits. However, they are associated with several immune-related adverse effects. While the cardiovascular (CV) risks of ICIs are well recognized, direct head-to-head comparisons of individual ICI agents remain underexplored. This study provides a comparative analysis of the CV adverse effects (CVAE) in lung cancer patients treated with pembrolizumab, durvalumab, and atezolizumab, addressing a critical gap in ICI safety profiles. Methods: A retrospective, propensity score-matched study was conducted using the TriNetX database. Patients with lung cancer between 2019 and 2024, treated with either pembrolizumab, atezolizumab, or durvalumab were included. Outcomes of interest were new-onset arrhythmias, heart failure (HF), myocarditis, pericarditis, coronary artery disease (CAD), and cardiac arrest. Propensity score matching accounted for demographics, comorbidities, and disease status. Results: A total of 2,475 patients on pembrolizumab, 650 on atezolizumab, and 825 on durvalumab met inclusion criteria. Propensity matching yielded 646 patients for pembrolizumab vs. atezolizumab, 820 for pembrolizumab vs. durvalumab, and 581 for atezolizumab vs. durvalumab comparisons. Pembrolizumab reduced new-onset arrhythmias by 9.6% compared to atezolizumab (RR 0.90 [95% CI: 0.82–0.99], p<0.05) but increased pericarditis risk by 32% (RR 1.32 [95% CI: 1.07–1.63], p<0.05). Compared to durvalumab, pembrolizumab showed a 42% higher cardiac arrest risk (RR 1.43 [95% CI: 1.01–2.03], HR 1.77 [95% CI: 1.22–2.55], p<0.05). Atezolizumab had a 24.7% lower HF risk (RR 0.75 [95% CI: 0.61–0.92], p<0.05), 21% lower pericarditis risk (RR 0.79 [95% CI: 0.63–0.98], p<0.05), and 25% lower CAD risk (RR 0.75 [95% CI: 0.58–0.96], p<0.05) compared to durvalumab. Conclusions: This study highlights significant variations in CVAE profiles among pembrolizumab, atezolizumab, and durvalumab. Atezolizumab demonstrated the most favorable CV safety profile, with lower risk of HF, pericarditis, and CAD compared to durvalumab, and reduced risk of pericarditis relative to pembrolizumab, albeit with a higher risk of new-onset arrhythmias. Pembrolizumab was associated with a higher risk of cardiac arrest compared to durvalumab. These findings emphasize the need for tailoring ICIs to individual CV risk factors, offering a framework for more personalized, safer treatment strategies in lung cancer management.