Trastuzumab plus chemotherapy is currently the standard first-line regimen for HER2 positive metastatic gastric or gastroesophageal junction adenocarcinoma. However, trastuzumab induces the expression of PD-L1 on tumor cells and may therefore cause the resistance to trastuzumab. A phase II trial was conducted to examine the efficacy of trastuzumab, chemotherapy plus pembrolizumab in HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. The objective response rate (ORR) was 87.5% (28/32) and the disease control rate (DCR) was 100% (32/32). At the data cut-off point, the median PFS was 11.4 months and the median OS was not reached. In the results of biomarker analysis, HER2 status was important for this combination regimen but PD-L1 level was not a predictor of PFS. These data indicated that the combination of trastuzumab, chemotherapy, and pembrolizumab may benefit more patients with HER2-positive metastatic esophagogastric adenocarcinoma. These promising safety and efficacy results led to the initiation of phase III Keynote-811 trial.
References: J Clin Oncol 37, 2019 (suppl 4; abstr 62)