The Zanidatamab Era in First-Line Treatment of HER2-Positive Gastric Cancer
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A 15-Year Standard in Gastric Cancer Is Changing: Survival Exceeds 2 Years with Zanidatamab and Immunotherapy
Approximately 20% of gastric and esophageal (gastroesophageal) cancers have an aggressive biology described as ‘HER2-positive’. For more than a decade, our standard treatment for these patients was ‘Trastuzumab + Chemotherapy’. However, the medical community was seeking a more effective option offering longer survival.
Announced at the ASCO Gastrointestinal Cancers Symposium 2026 (LBA285), HERIZON-GEA-01 trial results attracted attention. A new-generation targeted drug, Zanidatamab, produced far superior results to the previous standard, both alone and in combination with immunotherapy (Tislelizumab).
By showing that more than half the patients were still alive 2 years after starting treatment, this study marked a ‘historic achievement’ in gastric cancer.
HERIZON-GEA-01: A Major Comparison in 900 Patients
In this global Phase 3 trial, previously untreated (first-line) patients with HER2-positive advanced gastric/esophageal cancer — 914 patients — were divided into three groups:
- Group 1 (Triple Combination): Zanidatamab + Tislelizumab + Chemotherapy
- Group 2 (Double Combination): Zanidatamab + Chemotherapy
- Group 3 (Previous Standard/Control): Trastuzumab + Chemotherapy
Results: ‘Practice-Changing’ Differences
Median Overall Survival (OS)
The triple combination reduced mortality risk by 28% compared with the previous standard (HR: 0.72, P = .0043).
Time Without Disease Progression (PFS)
Other Important Findings
- Independence from PD-L1: Immunotherapy is normally expected to work only in PD-L1-positive tumors. In this study, however, adding Tislelizumab benefited both PD-L1-positive and negative patients. This is a very surprising and favorable finding.
- Duration of Response: In patients receiving the triple combination, the tumor-shrinkage response lasted an average of 20.7 months . With the previous treatment, it lasted only 8.3 months.
- Safety: The most common adverse effect was diarrhea, which was manageable. Serious adverse effects were somewhat more frequent in the triple arm (41% vs 20%), but not to a degree that caused treatment discontinuation.
- Elimova E, et al. Zanidatamab With or Without Tislelizumab Yields Clinically Meaningful Survival Benefit in HER2-Positive Advanced Gastroesophageal Adenocarcinoma (HERIZON-GEA-01). ASCO Gastrointestinal Cancers Symposium. 2026; Abstract LBA285.
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