Chemotherapy After Immune Checkpoint Inhibitor Exposure in Advanced Gastric Cancer: Clinical Evidence and Treatment Sequencing in the ICI Era.

purposeThe incorporation of immune checkpoint inhibitors (ICIs) into first-line therapy has changed the treatment landscape of advanced gastric and gastroesophageal junction cancer. This review summarizes the clinical evidence for chemotherapy after prior ICI exposure, discusses potential biological mechanisms, and considers practical treatment sequencing in the ICI era.

methodsWe conducted a targeted narrative review of PubMed/MEDLINE and major oncology congress proceedings through July 19, 2026. Original clinical studies reporting outcomes of systemic chemotherapy after prior ICI exposure in advanced gastric or gastroesophageal junction cancer were prioritized, with selected evidence from other tumor types and mechanistic studies included for context.

resultsRetrospective and observational studies suggest that chemotherapy after anti-PD-1 therapy can retain clinically meaningful activity, although the evidence is heterogeneous and largely non-randomized. Taxane plus ramucirumab is the most extensively studied post-ICI regimen, but available data in the contemporary first-line-ICI setting do not establish superiority over other guideline-supported second-line options. Whether favorable outcomes reflect true immunologic chemosensitization, residual immune activation interacting with subsequent cytotoxic or anti-angiogenic therapy, or patient selection remains unresolved.

conclusionCurrent evidence supports individualized selection among guideline-recommended second-line regimens, including taxane plus ramucirumab, single-agent taxane, and irinotecan, after first-line fluoropyrimidine/platinum plus ICI. Prospective post-ICI validation and biomarker-integrated studies are needed.