A related commentary discusses this research. Several factors, including the intratumoural heterogeneity of HER2, ethnicity of participants, tumour site, histology, clinical features, and chemotherapy backbone used, might explain these negative results. Future research should focus on identification and validation of predictive biomarkers to help select those patients with untreated HER2-positive metastatic gastric cancer who might benefit most from anti-HER2-targeted therapy.