The last 2 decades have seen a paradigm shift in the treatment landscape of metastatic gastric and gastroesophageal adenocarcinomas, with most of the progress occurring in recent years. Following the pivotal ToGA trial and the approval of trastuzumab for HER2-positive disease, the search for biomarkers has advanced exponentially. Currently, therapies are guided by key biomarkers such as HER2, PD-L1, dMMR/MSI-H, and, most recently, CLDN18.2. FGFR2b is emerging as a potential biomarker in this field. The most recent addition to this therapeutic arsenal is zolbetuximab. Two recent phase III trials have demonstrated survival benefits with the addition of zolbetuximab to frontline chemotherapy. A number of other biomarker-driven clinical trials are in progress, investigating new targeted agents that are expected to further transform the management of gastric or gastroesophageal adenocarcinoma.

The last 2 decades have seen a paradigm shift in the treatment landscape of metastatic gastric and gastroesophageal adenocarcinomas, with most of the progress occurring in recent years. Following the pivotal ToGA trial and the approval of trastuzumab for HER2-positive disease, the search for biomarkers has advanced exponentially. Currently, therapies are guided by key biomarkers such as HER2, PD-L1, dMMR/MSI-H, and, most recently, CLDN18.2. FGFR2b is emerging as a potential biomarker in this field. The most recent addition to this therapeutic arsenal is zolbetuximab. Two recent phase III trials have demonstrated survival benefits with the addition of zolbetuximab to frontline chemotherapy. A number of other biomarker-driven clinical trials are in progress, investigating new targeted agents that are expected to further transform the management of gastric or gastroesophageal adenocarcinoma.