Zanidatamab as First-Line Treatment for HER2-Positive Gastric Cancer: HERIZON-GEA-01 Results

New scientific data have emerged that could change the first-line treatment of HER2-positive gastric cancer and gastroesophageal junction cancer. In the international phase III HERIZON-GEA-01 study, the standard regimen of trastuzumab + chemotherapy was compared with zanidatamab-containing regimens in previously untreated patients with locally advanced unresectable or metastatic HER2-positive gastroesophageal adenocarcinoma. The study enrolled 914 patients.

The HERIZON-GEA-01 Study

For the zanidatamab + chemotherapy arm, median progression-free survival was 12.4 months versus 8.1 months with trastuzumab + chemotherapy. This corresponded to a 35% reduction in the risk of progression or death (HR 0.65; p<0.0001). For overall survival, at the time of interim analysis, there was a pronounced trend favoring zanidatamab (24.4 vs 19.2 months), but formal statistical significance was not reached at this data cut (HR 0.80; p=0.0564).

Why is this news truly important? Today, the first-line standard for HER2-positive advanced gastric cancer is built around HER2-directed therapy with chemotherapy, and HERIZON-GEA-01 is the first study to show that zanidatamab-containing regimens can improve outcomes compared with the trastuzumab-containing standard. At the ASCO international congress, improved disease control and overall survival were noted with zanidatamab-containing regimens.

Zanidatamab itself already has accelerated FDA approval, but in a different indication — for previously treated HER2-positive biliary tract cancer. For first-line gastroesophageal adenocarcinoma, the company announced plans to submit materials for an expanded indication in the first half of 2026 following the HERIZON-GEA-01 results.

When to Seek a Second Opinion

A repeat consultation is particularly warranted if you have HER2-positive gastric or gastroesophageal junction cancer and:

• you need to choose a first-line treatment
• you are being offered different regimens at different clinics
• there are doubts about HER2 status interpretation
• you want to understand how closely the proposed plan aligns with the latest data

What to Prepare Before Your Consultation

For the review to be truly useful, it is best to prepare in advance the histopathology report, HER2 immunohistochemistry results, PD-L1 data, discharge summaries from prior treatment (if any), and recent CT, MRI, or PET-CT. For choosing first-line treatment, the details matter. They determine how applicable the results of a new study are to a specific clinical situation.

Conclusion

The HERIZON-GEA-01 data represent one of the most important recent developments for HER2-positive gastric cancer. The study showed that zanidatamab-containing regimens can improve first-line outcomes compared with trastuzumab + chemotherapy.