AbstractBackgroundPrevious clinical trials indicated the addition of anti‐PD‐1 antibody remarkably improved the efficacy of trastuzumab and chemotherapy in patients with HER2‐positive gastric/gastroesophageal junction (GEJ) cancer. However, no real‐world experiences have been reported yet.MethodsWe retrospectively analyzed 1212 patients with gastric/GEJ cancer treated at Nanjing Drum Tower Hospital between 2019 and 2022. Among 138 patients with HER2‐positive gastric/GEJ cancer, 47 patients receiving at least two doses of the combination regimen with anti‐PD‐1 antibody, trastuzumab, and chemotherapy were recruited in the study population, and 38 out of 47 patients with measurable disease were included in the efficacy population. Progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were reported.ResultsIn the study population, 37 (78.7%) received the study therapy as a first‐line treatment. In the efficacy population, the ORR and DCR were 76.3% and 94.7%, respectively. The overall median PFS was 9.1 months (95% confidence interval [CI] 6.3–11.9 months). For the first‐line treatment, the mPFS was 10 months, and 7 months for the second‐line. Among 14 patients who failed the study treatment, three (21.4%) developed brain metastasis as the first failure site. No significant association was found between PFS and the expression of PD‐L1. 22.2% of patients developed grade 3 treatment‐related adverse events (TRAEs). No treatment‐related grade ≥4 adverse events or deaths occurred.ConclusionThis real‐world study validated the combination regimen's high efficacy and good tolerance in patients with HER2‐positive gastric/GEJ cancer. An increased incidence of brain metastasis was observed in patients who failed this regimen.