Proactive Diarrhea Management With Zanidatamab-Based Regimens

Drs Kim and Pereira address diarrhea, the most notable toxicity associated with zanidatamab-based regimens in HERIZON-GEA-01. Dr. Kim explains that diarrhea was common, typically occurred within the first week of treatment, and resolved quickly with mandatory loperamide prophylaxis, after which many patients were able to de-escalate antidiarrheal therapy. She notes that most trial patients received capecitabine-based chemotherapy, a known contributor to diarrhea, whereas most US patients receive FOLFOX. Dr. Pereira emphasizes distinguishing zanidatamab-related diarrhea from immune-mediated colitis. He notes that onset timing can guide management, since colitis typically emerges later and requires holding immunotherapy and starting steroids. Drawing on lessons from earlier-phase studies, he advises omitting the fluorouracil bolus when combining FOLFOX with zanidatamab and tislelizumab and starting prophylactic loperamide. He also recommends having care teams contact patients within the first days of treatment to identify and manage diarrhea early.