ASCO GI 2026: HERIZON-GEA-01 / Gastric/GEJ Cancer 01/30/2026

Ep. 3: HERIZON-GEA-01: Infusion and GI Management for Zanidatamab

Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD Young professional man in formal attire, smiling outdoors at a healthcare or medical conference, representing oncological research or updates from OncUpdates website. Geoffrey Ku, MD High-quality medical professional portrait for oncology updates, featuring a smiling female doctor in clinical attire, emphasizing expertise in cancer research and patient care, suitable for oncological informational content. Rutika Mehta, MD, MB, MPH Expert oncologist smiling in professional portrait, healthcare professional specializing in cancer treatment and research, wearing formal suit and glasses. Manish Shah, MD Experienced female oncology expert smiling, wearing a grey blazer and pink blouse, promoting cancer research and treatments at OncUpdates. Nataliya Uboha, MD, PhD

Key Points

  • Zanidatamab demonstrates strong efficacy in HER2-positive metastatic gastric and gastroesophageal junction (GEJ) cancer, supporting its adoption as a new frontline therapy.
  • Infusion reactions are manageable with standard precautions. Diarrhea is the primary toxicity, mitigated through proactive prophylaxis.
  • Patients with underlying severe bowel disease may require alternative therapy.

Zanidatamab Efficacy and Standard of Care

In a Clinical Insights panel discussion held at an event coinciding with the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute; Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center; Geoffrey Ku, MD, of Memorial Sloan Kettering Cancer Center; Rutika Mehta, MD, MB, MPH, of Weill Cornell Medicine; Manish Shah, MD, of Weill Cornell Medicine; and Nataliya Uboha, MD, PhD, of the University of Wisconsin School of Medicine and Public Health, reviewed evolving HER2-positive metastatic gastric cancer treatment. 

HERIZON-GEA-01 demonstrated that zanidatamab-based therapy improves progression-free and overall survival compared with historical trastuzumab regimens, supporting its adoption as a new frontline standard for most eligible patients. Although cross-trial comparisons remain necessary for some combinations, the panel largely agreed on zanidatamab’s superiority. The trial included zanidatamab with chemotherapy alone and combined with tislelizumab. Adding immunotherapy extended the duration of response to approximately 20 months, roughly double that observed without tislelizumab. 

Toxicity Management and Clinical Considerations

Diarrhea remains the most common and clinically relevant toxicity with zanidatamab, particularly when used with capecitabine and oxaliplatin chemotherapy. Prophylactic loperamide was standard in the trial and is recommended in practice, with ongoing monitoring during early cycles to adjust dosing as needed. Infusion reactions were generally infrequent, mostly grade 1 or 2, and manageable with slower infusion rates or premedication. 

For patients who experience severe diarrhea or frailty, dose adjustments or temporary chemotherapy discontinuation can optimize safety without compromising efficacy. HERIZON-GEA-01 also allowed stopping chemotherapy after 6 cycles, enabling long-term maintenance with zanidatamab, with or without tislelizumab, an approach with favorable toxicity in other biliary tract cancers.

Although zanidatamab is broadly applicable, certain populations require caution. Patients with significant underlying inflammatory bowel disease, such as Crohn disease or ulcerative colitis, may not tolerate therapy due to exacerbation of gastrointestinal toxicity, and immunotherapy is contraindicated in this group.