Selecting First-Line Therapy and Prioritizing Biomarkers in HER2-Positive GEA

Dr. Kim shares that she favors the zanidatamab triplet for patients with HER2-positive, PD-L1-negative disease. She acknowledges that HERIZON-GEA-01 did not directly compare the regimen with pembrolizumab, trastuzumab, and chemotherapy in PD-L1-positive disease. For patients with pre-existing diarrhea or limited tolerance for dehydration, both physicians note that the KEYNOTE-811 regimen remains a reasonable option, and Dr. Pereira points out that both approaches are included in current NCCN guidelines. Dr. Kim describes starting with the newer regimen and de-escalating to a trastuzumab-based approach if toxicity becomes difficult to manage. The physicians emphasize comprehensive biomarker testing in advanced disease, including MSI status, PD-L1, HER2, and claudin. Dr. Kim prioritizes HER2-directed therapy when multiple biomarkers are positive, given the strength of the supporting data. Dr. Pereira closes by describing the zanidatamab triplet as his new first-line standard for HER2-positive disease.