Immune checkpoint inhibition in Epstein-Barr virus associated gastric cancer: a case report highlighting the role of biomarker-driven treatment selection

Gastroesophageal adenocarcinoma (GEA) represents a heterogenous disease with poor prognosis, in which biomarker-driven strategies have gained relevance to optimize treatment selection. Epstein-Barr virus positive GEA (EBV-GEA) is an immune-enriched molecular subtype defined by TCGA suggested to have potential sensitivity to immune checkpoint inhibitors. However, clinical evidence supporting the efficacy of immunotherapy in this subgroup remains limited, and EBV testing is not yet considered a validated biomarker in international clinical guidelines. We report a case of a 74-year-old male with locally advanced, HER-2 negative, mismatch repair-proficient, EBV-positive gastric adenocarcinoma, with high PD-L1 expression (CPS 69), who experienced disease progression during perioperative FLOT chemotherapy. The patient subsequently received first-line treatment with nivolumab plus FOLFOX, achieving a marked radiological response. Salvage surgery revealed a complete pathological response and no further treatment with nivolumab was administered after surgery. This case illustrates the potential benefit of immunotherapy in EBV-positive gastric cancer, even in the microsatellite-stable setting. The overlap of biomarkers in this patient may have contributed to immune response, highlighting the importance of comprehensive molecular profiling in GEA and supporting EBV status as a promising predictor of immunotherapy benefit.