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

This discussion summarizes the KEYNOTE-811 trial, which evaluated the addition of pembrolizumab to trastuzumab and platinum-based chemotherapy for patients with previously untreated, HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. The discussion highlights that this randomized study demonstrated a significant improvement in objective response rate, its primary early endpoint, with pembrolizumab leading to higher rates of rapid and deep tumor responses compared with trastuzumab and chemotherapy alone. Updated analyses have also shown a progression-free survival advantage and continued durability of response, with the greatest benefit observed among patients whose tumors express PD-L1, while overall survival results remain immature. The safety profile of the pembrolizumab-containing regimen was consistent with expectations for PD-1 inhibitors in combination with HER2-targeted therapy and chemotherapy, with no new safety signals reported. This segment underscores how KEYNOTE-811 has meaningfully influenced first-line treatment strategies for HER2-positive advanced gastric and GEJ cancers.