Cardiovascular outcomes of durvalumab versus pembrolizumab in gastric cancer: A propensity-matched TriNetX analysis.

e24017 Background: Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis are increasingly incorporated into gastric cancer treatment. Although rare, ICI-associated myocarditis is highly lethal and often presents early. PD-1 inhibition with pembrolizumab blocks both PD-L1 and PD-L2, resulting in broader immune activation, whereas PD-L1 inhibition with durvalumab preserves PD-1/PD-L2 signaling and may limit immune-mediated cardiotoxicity. In a population with substantial baseline cardiovascular risk, defining differential cardiovascular effects between these agents is clinically essential. Methods: A retrospective TriNetX U.S. Collaborative Network analysis compared cardiovascular outcomes among patients with gastric cancer treated with pembrolizumab versus durvalumab over follow-up periods of 1 year, 3 years, and lifetime. Propensity score matching was performed to balance demographics and baseline cardiovascular, secondary metastasis and metabolic comorbidities, including diabetes mellitus, hypertension, obesity, dyslipidemia, liver fibrosis, and cirrhosis. Outcomes assessed included all-cause mortality, stroke, major adverse cardiovascular events, heart failure, and arrhythmias, evaluated using time-to-event analyses. Results: The matched cohorts each comprised 327 individuals, with balanced baseline demographic and cardiovascular characteristics. Durvalumab was consistently associated with lower mortality and MACE risk across all time horizons (all p < 0.0001). (Table 1) Rates of stroke, heart failure, myocarditis, pericarditis, and arrhythmia were low across all time horizons and did not differ significantly between treatment groups. Conclusions: In a propensity-matched real-world cohort of patients with gastric cancer, durvalumab was associated with significantly lower all-cause mortality and MACE at 1-year, 3-year, and lifetime follow-up compared with pembrolizumab, Although limited by the observational design and potential residual confounding, these findings suggest a favorable survival and cardiovascular risk profile for durvalumab ( PD – L1) in this population and support the need for prospective and randomized studies to confirm these results. Cardiovascular outcomes in propensity-matched gastric cancer cohorts. Outcome Time Horizon Durvalumab Risk (%) Pembrolizumab Risk (%) Risk Ratio (95% CI) p-value Death 1 year 15.95 36.50 0.44 (0.33–0.58) <0.0001 3 years 18.10 49.08 0.37 (0.29–0.48) <0.0001 Lifetime 18.10 51.23 0.35 (0.27–0.46) <0.0001 MACE 1 year 17.91 38.64 0.46 (0.35–0.62) <0.0001 3 years 20.27 52.54 0.39 (0.30–0.50) <0.0001 Lifetime 20.27 54.58 0.37 (0.29–0.48) <0.0001