Managing Diarrhea and Other Adverse Events on Zanidatamab-Based Regimens

In this episode, Dr. Wainberg, Dr. Shameem, and Dr. Elimova discuss practical management of zanidatamab's toxicity profile, with diarrhea as the central issue. Dr. Wainberg frames the problem: zanidatamab produces early-onset gastrointestinal toxicity unusual for an antibody, and HERIZON-GEA-01 incorporated a prophylactic strategy that Dr. Shameem describes as having reduced the incidence of high-grade diarrhea after being amended into the phase 2 program.

Dr. Shameem's protocol, informed by his zanidatamab experience in biliary tract cancer, is loperamide 4 mg twice daily for at least the first 7 days, with the option to extend or add a second antidiarrheal if symptoms persist. He stresses that counseling patients to expect diarrhea is as important as the prophylaxis itself. Loperamide is cheap and widely available, making this practical for community settings.

Dr. Elimova adds that she instructs patients to call at the first sign of diarrhea even on loperamide, and her nursing team makes proactive calls at or before the one-week mark. Diarrhea typically occurs early and resolves by 3 weeks. If it develops on a weekend while a patient is on capecitabine, she instructs them to stop capecitabine and regroup afterward. For patients she is more worried about, she may arrange home IV hydration. Dr. Wainberg notes that when tislelizumab is in the regimen, immune-related diarrhea and colitis are important to stay on top of.

Dr. Elimova notes that infusion reactions are more frequent but predominantly grade 1–2 and very manageable, and LVEF monitoring follows standard practice with echocardiograms every 3 months.

In the next episode, “HER2 Heterogeneity, Subclonal Biology, and Retesting at Progression,” Dr. Shah discusses how subclonal HER2 biology distinguishes gastric from breast cancer and what this means for retesting after progression.