Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer.
Summary
An open-label, phase 3 trial evaluated zanidatamab, a HER2-targeted bispecific antibody, with or without tislelizumab (anti-PD-1), combined with chemotherapy, as first-line treatment for HER2-positive advanced gastroesophageal adenocarcinoma. Patients were randomized to receive zanidatamab-tislelizumab-chemotherapy, zanidatamab-chemotherapy, or trastuzumab-chemotherapy. Both zanidatamab-tislelizumab-chemotherapy and zanidatamab-chemotherapy arms demonstrated significantly longer progression-free survival (median 12.4 months for both) compared to trastuzumab-chemotherapy (8.1 months). Overall survival was also longer with zanidatamab-tislelizumab-chemotherapy (26.4 months) than with trastuzumab-chemotherapy (19.2 months). Diarrhea was the most common grade 3 or higher adverse event.
Analysis
This study is of paramount importance as it demonstrates that zanidatamab, either alone or in combination with tislelizumab and chemotherapy, significantly improves progression-free survival in patients with HER2-positive advanced gastroesophageal adenocarcinoma compared to standard trastuzumab-chemotherapy. The improved overall survival observed with the triple combination of zanidatamab-tislelizumab-chemotherapy is particularly promising. These results could redefine first-line treatment for this patient population, offering new, more effective therapeutic options and potentially improving patient prognosis.