The Evolving First-Line Landscape in HER2-Positive GEA

Allan Lima Pereira, MD, of Moffitt Cancer Center, and Sunnie Kim, MD, of University of Colorado Cancer Center, open their discussion by reviewing how first-line treatment for HER2-positive gastroesophageal adenocarcinoma (GEA) has evolved. Dr. Kim traces the path from the ToGA trial, which established trastuzumab plus chemotherapy as a standard of care, through a series of negative trials of HER2-directed agents borrowed from breast cancer, to KEYNOTE-811, which added pembrolizumab with benefit ultimately limited to patients with PD-L1-positive disease. She then outlines the design of the pivotal HERIZON-GEA-01 trial, which randomly assigned patients to zanidatamab plus chemotherapy with or without tislelizumab vs trastuzumab plus chemotherapy, with progression-free and overall survival as primary end points. The physicians discuss key design considerations, including a control arm without immunotherapy, which reflects that the trial was designed before KEYNOTE-811 changed the standard, and the global makeup of the trial population.