Adverse events with PD-1 inhibitors in gastric cancer: A real-world comparative study.

Abstract

423 Background: Programmed death-1 (PD-1) inhibitors such as nivolumab and pembrolizumab have emerged as therapeutic options in gastric cancer, but their impact on survival and treatment-related adverse events compared to non-immunotherapy regimens remains unclear. Methods: Using the TriNetX US Collaborative Network of 71 healthcare organizations, we conducted a retrospective propensity score–matched cohort study. Cohort 1 included patients with gastric cancer treated with PD-1 inhibitors (n=5,625; matched n=2,954), and Cohort 2 comprised patients with gastric cancer not treated with PD-1 blockade (n=86,722; matched n=2,954). Outcomes assessed over 5 years included overall mortality, gastrointestinal (GI) bleeding, pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, and ischemic coronary artery disease (CAD). Kaplan–Meier analyses, log-rank tests, and hazard ratios (HRs) were used for comparison. Results: After matching, PD-1 treatment was associated with increased risks of pulmonary embolism (HR 1.25, 95% CI 1.07–1.45, p =0.005) and stroke (HR 1.46, 95% CI 1.13–1.89, p =0.003). Mortality was higher in the PD-1 cohort (median survival 511 vs. 592 days; HR 1.10, 95% CI 1.03–1.19, p =0.007). No significant differences were observed for upper/lower GI bleeding, DVT, or ischemic CAD. Conclusions: In this real-world analysis, PD-1 inhibitor use in gastric cancer was associated with higher risks of certain thromboembolic and cerebrovascular events including stroke and PE. These findings highlight the need for careful patient selection and monitoring during PD-1–based immunotherapy.