Gastroesophageal adenocarcinoma (GOAC) is among the leading causes of cancer mortality worldwide. Patients with metastatic HER2-negative GOAC, which accounts for about 75% of cases, have relied exclusively on cytotoxic chemotherapy for decades, leading to suboptimal survival. The introduction of immune checkpoint inhibitors significantly improved survival across molecular subtypes. The current recommended first-line treatment includes a combination of oxaliplatin, a fluoropyrimidine, and a PD-1 inhibitor (programmed death protein 1 antibody) for patients with HER2-negative metastatic GOAC, especially with positive PD-L1 status. Oxaliplatin is usually discontinued after an induction period of four to six months to optimize quality of life and avoid neurologic and hematologic toxicity associated with the cumulative dose. PD-1 inhibition lasts longer.