Evolving First-Line Options in HER2-Positive Gastroesophageal Adenocarcinoma

In this OncLive News Network program, Allan Lima Pereira, MD, of Moffitt Cancer Center, and Sunnie Kim, MD, of University of Colorado Cancer Center, discuss first-line treatment for HER2-positive gastroesophageal adenocarcinoma (GEA) following the pivotal HERIZON-GEA-01 trial and the FDA approval of zanidatamab-based regimens. The physicians trace the evolution of the first-line landscape from the ToGA and KEYNOTE-811 trials and review the design and efficacy results of HERIZON-GEA-01. They also examine how HER2 expression shapes the FDA-approved indications. They explore the unexpected PD-L1 subgroup findings, the rationale for adding tislelizumab, and practical strategies for preventing and managing diarrhea, including how to distinguish it from immune-mediated colitis. The discussion closes with guidance on selecting between the zanidatamab and KEYNOTE-811 regimens, the importance of comprehensive biomarker testing, and how to prioritize HER2-directed therapy when multiple biomarkers are positive.