Serplulimab with FOLFOX showed disease control in AFP-producing gastric adenocarcinoma with liver metastases.

AFP-producing gastric carcinoma (AFPGC) is an uncommon but clinically aggressive subset of gastric cancer with a strong propensity for liver metastasis. Serum alpha-fetoprotein (AFP) is often markedly elevated, whereas tumor AFP immunostaining can be negative, which may complicate recognition and classification. A 67-year-old man presented with epigastric pain. Contrast-enhanced computed tomography showed gastric wall thickening and multiple hepatic metastases. Endoscopic biopsy revealed a poorly differentiated adenocarcinoma with hepatoid/enteroblastic differentiation features. Immunohistochemistry was positive for SALL4, glypican-3, pan-cytokeratin, and nuclear CDX2, and negative for AFP and neuroendocrine markers. Helicobacter pylori testing was negative. Baseline serum AFP was markedly elevated. After intolerance to oral S-1, the patient received FOLFOX plus the PD-1 inhibitor serplulimab, followed by maintenance serplulimab. Treatment was well tolerated, without immune-related adverse events requiring systemic corticosteroids or treatment interruption. Serial magnetic resonance imaging demonstrated marked and sustained shrinkage of hepatic lesions. A RECIST v1.1–based assessment, using available measurements of measurable target lesions, was consistent with a partial response. Serum AFP rapidly normalized and remained within the reference range during maintenance therapy, paralleling the radiologic response. This case suggests that chemo-immunotherapy with platinum–fluoropyrimidine chemotherapy plus PD-1 blockade may yield substantial and durable disease control in selected patients with metastatic AFPGC, even when tumor AFP staining is negative. AFP kinetics provided a rapid and reproducible on-treatment biomarker that complemented imaging. Given the paucity of prospective data in AFP-high gastric cancer, this report is hypothesis-generating and supports further evaluation of chemo-immunotherapy in larger studies.