Abstract
<title>Abstract</title> <p>Background Immune checkpoint inhibitors (ICIs) have revolutionized gastrointestinal (GI) cancer therapy, yet immune-related interstitial lung disease (ILD) remains a rare but fatal complication. While well-characterized in lung cancer, the specific clinical profile and risk patterns of ICI-ILD in GI malignancies remain insufficiently explored. This study evaluates real-world safety signals and manifestations of ICI-induced ILD in the GI cancer population. Methods A retrospective pharmacovigilance analysis was conducted using the FAERS database (2015–2025). Disproportionality metrics (ROR, PRR, and EBGM) were employed to quantify pulmonary safety signals. Results A total of 588 ICI-ILD cases were identified, primarily involving gastric (32.7%) and esophageal (22.8%) cancers, with nivolumab (58.3%) as the most frequently implicated agent. Gender-stratified analysis revealed that while males constituted the majority of cases, females exhibited higher relative risk signals (ROR) for specific agents, such as avelumab. Temporally, ipilimumab demonstrated a highly concentrated early-onset risk window within the first 30 days, whereas PD-1/PD-L1 inhibitors showed a more prolonged risk distribution. Within the serious adverse event population, ROR signals exhibited marked intra-class variation. Furthermore, clinical manifestations and signal intensities demonstrated distinct regional specificities across different geographic areas. Conclusion ICI-related ILD in GI oncology demonstrates distinct age, gender, and agent-specific risk profiles. Given the high fatality rate and heterogeneous TTO, risk-stratified monitoring is essential. These findings offer critical evidence to optimize immunotherapy safety in gastrointestinal oncology.</p>