Worldwide gastric cancer is the 5th most common cancer and the 4th leading cause of cancer deaths. Its highest incidence rates are in east Asia and eastern Europe with low incidence rates in North America and Northern Europe. Overall, gastric cancer has a poor prognosis and often demonstrates regional spread to lymph nodes (in about a quarter of the patients) and distant spread (metastatic disease), in about a third of the patients at the time of diagnosis.
Over the past several years, there have been increasing requests for biomarker testing in gastric and gastroesophageal junction (GEJ) adenocarcinomas. The standard first line treatment for patients with locally advanced inoperable or metastatic gastric adenocarcinoma has been chemotherapy, with a median overall survival of 1 year. Combining targeted therapies with chemotherapy can improve survival. In patients with Her2 positive gastric and GEJ adenocarcinoma, trastuzumab has been approved in combination with chemotherapy. In these patients, assessment of HER2 overexpression in the tumor using immunohistochemistry or in-situ hybridization is recommended by the National Comprehensive Cancer Network (NCCN). All patients with newly diagnosed gastric cancer should also undergo biomarker testing for identification of MSI-H/dMMR gastric adenocarcinoma in consideration for administration of immunotherapy. Checkpoint inhibitor therapy is utilized in combination with chemotherapy as first line therapy in some countries, however, efficacy is mainly in patients with a PD-L1 CPS score of 5 or more. For patients who have HER2 negative disease, and who have a PD-L1 CPS less than 5, an emerging therapeutic target is high Claudin-18 isoform 2 (CLDN18.2) expression.
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