Current Targeted Therapies in HER2-Positive Gastric Adenocarcinoma

Abstract

Gastric cancer is one of the most common types of cancer in the world, usually diagnosed at an advanced stage. Despite the advances in specific anticancer agents' development, the survival rates remain modest, even in early stages. In 15%-20% of cases, the human epidermal growth factor receptor 2 (HER2) overexpression was identified. We conducted a general review to summarize the progress that has been made in the targeted treatment of HER2-positive esogastric junction or gastric adenocarcinoma. According to our findings, trastuzumab is the only validated anti-HER2 agent in locally advanced or metastatic disease and its adjuvant effectiveness is assessed in a RTOG phase III study. In a previously treated advanced disease, the maytansine derivate TDM 1 failed to be approved as a second-line regimen, and the tyrosine kinase inhibitor, lapatinib, shows modest results. The antiangiogenics have not been analyzed in specific populations and targeting the mesenchymal-epithelial transition factor (MET) receptor, overexpressed in up to 46% of the advanced disease, seems encouraging. Regarding the checkpoint inhibitors, based on KEYNOTE 059 multilevel ongoing trial, stratified according to the HER2 and programmed death-ligand (PD-L) 1 status, pembrolizumab was approved for third-line treatment of gastric or gastroesophageal junction adenocarcinoma.

Keywords: HER2 overexpression; gastric cancer; resistance mechanism; targeted therapy; trastuzumab.