MONDAY, Jan. 12, 2026 (HealthDay News) -- For patients with human epidermal growth factor receptor 2-positive (HER2-positive) metastatic or locally advanced unresected gastroesophageal adenocarcinoma (mGEA), zanidatamab and chemotherapy, with or without tislelizumab, may prolong survival compared with trastuzumab + chemotherapy, according to a study presented at the American Society of Clinical Oncology annual Gastrointestinal Cancers Symposium, held from Jan. 8 to 10 in San Francisco.
Elena Elimova, M.D., from the Princess Margaret Cancer Centre in Toronto, and colleagues conducted an open-label phase 3 trial in 914 patients with previously untreated HER2-positive mGEA. Patients were randomly assigned to receive zanidatamab + chemotherapy, zanidatamab + chemotherapy + tislelizumab, or trastuzumab + chemotherapy.
After a median follow-up of 26 months, the researchers found that progression-free survival was significantly prolonged in zanidatamab-containing arms versus trastuzumab + chemotherapy (median progression-free survival 12.4 and 12.4 months, respectively, versus 8.1 months; hazard ratios [95 percent confidence intervals], 0.65 [0.52 to 0.81] for zanidatamab + chemotherapy and 0.63 [0.51 to 0.78] for zanidatamab + chemotherapy + tislelizumab). In terms of overall survival, there was a trend toward improvement for zanidatamab + chemotherapy, while a significant benefit was seen for zanidatamab + chemotherapy + tislelizumab (median overall survival, 24.4 and 26.4 months, respectively, versus 19.2 months; hazard ratios, 0.80 [0.64 to 1.01; at interim analysis] and 0.72 [0.57 to 0.90], respectively). Grade 3 or higher treatment-related adverse events occurred in 71.8, 59.0, and 59.6 percent of patients treated with zanidatamab + chemotherapy + tislelizumab, zanidatamab + chemotherapy, or trastuzumab + chemotherapy, respectively.
"This is the first phase 3 trial to demonstrate a benefit for a novel HER2-targeted therapy compared to trastuzumab as part of a combination regimen in HER2-positive first-line treatment for these patients," Elimova said in a statement.
The study was sponsored by Jazz Pharmaceuticals, the manufacturer of zanidatamab, conducted jointly with BeOne Medicines.