Modern Management of Her2-Positive Gastric Cancer: Clinical Insights and Evidence From Trials

Introduction: Gastric cancer (GC) remains a major global health issue, ranking among the leading causes of cancer-related deaths worldwide. Despite improvements in diagnostic methods, many patients are still diagnosed at an advanced stage. The discovery of HER2 overexpression in approximately 15–20% of GC cases introduced targeted therapy into clinical practice. The ToGA trial established trastuzumab combined with chemotherapy as the first-line treatment for HER2-positive advanced GC, significantly improving survival. Aim of the study: This review summarizes current knowledge about the epidemiology, clinical staging, and treatment strategies for advanced gastric cancer, with particular focus on HER2-positive tumors. It also outlines the evolution of HER2-targeted therapies and discusses novel agents and clinical trials that may shape future management. Material and methods: The review was based on data collected from PubMed and Google Scholar using key terms: gastric cancer, HER2-positive, chemotherapy, targeted therapy, immunotherapy, clinical trials, ToGA, T-DXd, ZW25, KN026. Conclusion: GC is a complex and heterogeneous disease that requires accurate staging and individualized treatment strategies. While traditional chemotherapy remains the foundation of care, the incorporation of targeted therapies and immune checkpoint inhibitors has changed the treatment landscape. HER2 remains a critical biomarker, with newer agents such as trastuzumab deruxtecan, zanidatamab, and KN026 showing promising results. Continued molecular profiling and participation in clinical trials are essential for improving outcomes in HER2-positive GC patients.