KEYNOTE-811: Efficacy and Safety of Pembrolizumab + Trastuzumab + Chemotherapy in HER2+ Gastric/GEJ Adenocarcinoma

This discussion reviews the KEYNOTE-811 trial, which evaluates the addition of pembrolizumab to trastuzumab and chemotherapy in the first-line treatment of HER2-positive gastric and gastroesophageal junction (GEJ) adenocarcinoma. The discussion highlights that the combination demonstrated a substantial improvement in objective response rate compared with trastuzumab and chemotherapy alone, which supported its accelerated regulatory approval. Exploratory analyses have indicated that responses appear particularly strong in tumors expressing PD-L1, suggesting potential biological synergy between HER2-targeted therapy and PD-1 blockade. The segment also notes that the safety profile of the pembrolizumab-containing regimen has been consistent with expectations, with no new or unexpected toxicities observed, including comparable rates of cardiac adverse events across arms. As overall survival results remain immature, the panel emphasizes that KEYNOTE-811 has played an important role in shaping current treatment strategies for patients with HER2-positive advanced gastric and GEJ cancers.