S18 Ep34: Integrating Precision Pathways in HER2+ Gastroesophageal Adenocarcinoma—Testing, Treatment, and Supportive Care

Advanced gastroesophageal adenocarcinoma management requires mandatory testing for HER2, Claudin 18.2, mismatch repair deficiency, and PD-L1 to guide targeted therapy. Clinical evidence establishes the triplet regimen of zanidatamab, tislelizumab, and chemotherapy as a new standard of care, though clinicians must proactively manage treatment-related diarrhea through loperamide prophylaxis and chemotherapy dose adjustments. Because HER2 expression can be lost during therapy, retesting at disease progression is essential to confirm eligibility for subsequent treatments like trastuzumab deruxtecan. While T-DXd offers significant efficacy in the second-line setting, its use necessitates careful monitoring for interstitial lung disease and cardiomyopathy. Experts Sunnie Kim and Geoffrey Ku emphasize that while circulating tumor DNA remains investigational, comprehensive biomarker profiling remains the cornerstone for optimizing patient outcomes and navigating the emerging therapeutic landscape in metastatic disease.