Pembrolizumab vs nivolumab plus chemotherapy in metastatic gastric cancer: TriNetX propensity score–matched analysis.

e16066 Background: Pembrolizumab and nivolumab are PD-1 inhibitors used with chemotherapy for first-line HER2-negative advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma; comparative real-world outcomes are limited. We performed a propensity score-matched (PSM) analysis comparing OS and safety in the federated TriNetX Research Network. Methods: Retrospective cohort. Adults ( > = 18) with advanced/metastatic gastric cancer (ICD-10 C16 with C77-C79) treated with pembrolizumab (C1) or nivolumab (C2) plus platinum-fluoropyrimidine; index was first PD-1 dose. Cohorts were 1:1 PSM on demographics, comorbidities (hypertension, diabetes, CKD, cardiovascular disease), baseline hemoglobin, and TNM stage. Primary: all-cause mortality. Secondary: noninfective colitis, AKI, sepsis, pneumonia, acute respiratory failure, neutropenia, anemia, GI hemorrhage, VTE. Timepoints: 3m, 6m, 205d, 1y, 2y, 3y, and 5y. Statistical analyses: Kaplan–Meier (log-rank), Cox regression, and t-tests (event instances). Results: After PSM, n = 153/cohort; baseline was balanced (all SMD < 0.1): age 57.3±13.6 vs 57.5±13.0 years; White 66.0% vs 64.1%; secondary lymph node involvement 50.3% vs 45.8%; hypertension 48.4% vs 47.7%; anemia 47.1% vs 45.8%; diabetes 20.9% vs 20.3%. Median follow-up was 226d (IQR 485) for C1 and 354d (IQR 560) for C2. Mortality was higher with C1 at 205d (43.4% vs 34.4%; HR 1.448, 95% CI 1.007–2.083; log-rank P = 0.0447), with nonsignificant elevations at 3m (22.3% vs 15.0%; HR 1.599; P = 0.085), 6m (37.5% vs 31.1%; HR 1.368; P = 0.110), and 1y (53.3% vs 46.4%; HR 1.368; P = 0.054); no differences at 2y (64.5% vs 64.2%; HR 1.229; P = 0.150), 3y (69.1% vs 71.5%; HR 1.164; P = 0.268), or 5y (71.7% vs 72.9%; HR 1.161; P = 0.270). Noninfective colitis was lower in C1, significant at 3y (16.3% vs 25.5%; risk difference P = 0.049) and 5y (16.3% vs 26.1%; P = 0.036), while HR remained non-significant (5y HR 0.714, 95% CI 0.433–1.177; P = 0.184). Sepsis incidence was similar, but C1 had fewer mean sepsis episodes at 6m (1.2 vs 2.3; P = 0.008), 205d (1.3 vs 2.2; P = 0.010), 2y (1.6 vs 3.5; P = 0.022), 3y (1.6 vs 3.5; P = 0.020), and 5y (1.6 vs 3.5; P = 0.020). No differences were observed for AKI (5y 32.7% vs 37.9%; P = 0.339), pneumonia (5y 26.1% vs 27.5%; P = 0.796), neutropenia (5y 22.2% vs 29.4%; P = 0.151), anemia (5y 48.2% vs 48.2%; P = 1.000), GI hemorrhage (5y 19.0% vs 19.0%; P = 1.000), or VTE (5y 17.2% vs 24.0%; P = 0.163). Conclusions: In this real-world PSM analysis, pembrolizumab plus chemotherapy showed higher 205-day mortality vs nivolumab plus chemotherapy, while 2–5-year survival was similar. Pembrolizumab showed lower noninfective colitis rates and fewer recurrent sepsis episodes. The early survival difference warrants evaluation for confounding (PD-L1/HER2 status) and early toxicity management; prospective head-to-head trials are needed.