Advanced Gastroesophageal Adenocarcinoma: Real-World Benefit From Immunotherapy Depends on PD-L1: The Oncologist | October 2026

What Did the Study Find?

This contemporary Flatiron database study evaluated 2,340 patients with advanced/metastatic HER2-negative gastric, GEJ or esophageal adenocarcinoma treated in the US between 2021 and 2025.

• IO + FOLFOX/CAPOX became the most common first-line regimen, used in 31.6% overall.
• Among patients with PD-L1 CPS ≥1, its use increased to 47.6%.
• Compared with chemotherapy alone, IO + chemotherapy was associated with longer real-world OS (12.3 vs 11.3 months; HR 0.81).
• Time to next treatment/death improved (8.0 vs 6.1 months), as did treatment duration (6.0 vs 3.0 months).
• Crucially, the outcome advantage was driven by patients with CPS ≥1.
• In CPS <1 tumors, no outcome advantage with adding immunotherapy was observed.
• Since 2024, zolbetuximab + chemotherapy has increasingly entered practice, particularly in tumors with lower PD-L1 expression.

Why Does It Matter?

First-line gastroesophageal cancer treatment is moving away from a universal chemotherapy backbone toward biomarker-defined treatment selection.

GastroAGI Takeaway

The key real-world message is not simply “add immunotherapy”—it is “test before you treat.” PD-L1 status meaningfully separated patients who appeared to benefit from IO + chemotherapy, while emerging CLDN18.2-directed therapy is further reshaping first-line choices. Despite these advances, median survival remained only about one year, highlighting the substantial residual therapeutic need.