The Phase 3 HERIZON-GEA-01 trial showed that zanidatamab-hrii (Ziihera)-based regimens significantly improved outcomes for patients with previously untreated HER2-positive advanced gastric, gastroesophageal junction, and esophageal cancers.
The study enrolled 914 patients who received either zanidatamab plus tislelizumab and chemotherapy, zanidatamab plus chemotherapy, or standard trastuzumab plus chemotherapy. At a median follow-up of 25.9 months, both zanidatamab regimens improved progression-free survival compared with trastuzumab. Median progression-free survival reached 12.4 months in both zanidatamab groups versus 8.1 months with trastuzumab.
The triplet regimen also improved overall survival to 26.4 months, compared with 19.2 months in the control group, reducing the risk of death by 28%. Response durability was also longer with zanidatamab, especially in the triplet arm, where median duration of response reached 20.7 months.
Side effects were more frequent with zanidatamab combinations, particularly diarrhea and immune-related toxicities. Severe adverse events occurred in more than 80% of patients receiving the triplet regimen, and treatment discontinuations were more common than with trastuzumab.