Adverse events associated with immune checkpoint inhibitors in combination with chemotherapy in lung cancer: a real-world analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed lung cancer treatment, but clinical trials often miss rare, life-threatening toxicities and safety patterns in complex combinations. Real-world pharmacovigilance is essential to identify toxicity profiles in unselected populations. This study aimed to characterize adverse event reporting patterns associated with ICI monotherapy and ICI-based combination regimens in lung cancer using real-world data. METHODS: We analyzed 34,223 adverse event reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database (Q1 2016-Q3 2025) for pembrolizumab, atezolizumab, and nivolumab and their combinations. Disproportionality analysis, time-to-onset, and stratified analysis were conducted. RESULTS: Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors primarily caused endocrine and respiratory toxicities; ipilimumab caused dermatologic and hepatobiliary effects. Stress cardiomyopathy occurred across all agents, with pembrolizumab showed highest disproportionality signal. Males on atezolizumab had 73% lower odds of reported stress cardiomyopathy [odds ratio (OR) =0.27, P<0.01]. Combination-regimen analyses showed heterogeneous reporting profiles. For example, pembrolizumab-chemotherapy was associated with an earlier onset of duodenitis, atezolizumab-bevacizumab-platinum was uniquely associated with duodenal ulcer hemorrhage, and ventricular fibrillation was highlighted in by nivolumab-ipilimumab combination. CONCLUSIONS: ICI toxicity is highly regimen-specific and combination therapy was associated with a shorter reported time-to-onset and increased odds of reporting cardiac and gastrointestinal events, informing tailored surveillance strategies.