Real-world treatment landscape and clinical outcomes in first-line advanced or metastatic gastroesophageal adenocarcinoma in the United States.

BACKGROUND: Contemporary real-world evidence in advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma (GC/GEJC/EAC) remains limited. This study evaluated real-world treatment patterns and clinical outcomes in patients with advanced GC/GEJC/EAC treated with first-line therapy in the US. PATIENTS AND METHODS: Treatment patterns were assessed in adults from the Flatiron database with advanced or metastatic HER2-negative GC/GEJC/EAC who initiated first-line treatment between May 1, 2021, and July 31, 2025 (overall cohort). Clinical outcomes were assessed using the Kaplan-Meier method in a subcohort with ≥6 months of follow‑up. RESULTS: Among 2340 eligible patients, the most common first-line regimen was IO+FOLFOX/CAPOX (31.6%). This regimen was used in 47.6% of patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 expression. Starting in 2024, zolbetuximab+FOLFOX/CAPOX was administered more frequently in patients with CPS <1 versus ≥1 (6.1% vs 1.9%) and CPS <5 versus ≥5 (4.6% vs 0.8%) expression. In the subcohort (n=2117), IO+FOLFOX/CAPOX versus FOLFOX/CAPOX was associated with significantly longer median (months; hazard ratio [95% CI]) real-world overall survival (12.3 vs 11.3; 0.81 [0.69-0.94]), time to next treatment or death (8.0 vs 6.1; 0.64 [0.55-0.75]), and time to treatment discontinuation (6.0 vs 3.0; 0.54 [0.47-0.63]). Differences in outcomes were driven by patients with CPS ≥1 expression, with no differences in patients with CPS <1 expression. CONCLUSIONS: IO+FOLFOX/CAPOX was the most frequent first-line regimen in advanced or metastatic GC/GEJC/EAC and showed improved real-world outcomes versus FOLFOX/CAPOX. Despite these gains, overall survival remains poor, underscoring unmet needs and the importance of biomarker-informed treatment selection.