Pembrolizumab plus trastuzumab and chemotherapy has established a new first-line standard of care for patients with HER2-positive, PD-L1 CPS ≥1 metastatic gastric or gastroesophageal junction adenocarcinoma. Nonetheless, primary and acquired resistance driven by HER2 heterogeneity, immune evasion, and dynamic molecular evolution remain major challenges. Next-generation HER2-targeted therapies, including bispecific antibodies, novel antibody - drug conjugates, and dual HER2 antibodies will be crucial to further improve outcomes in this population.
Seguchi et al. (2026) studied this question.