Advances in the Management of HER2-positive Advanced Gastric and Gastroesophageal Junction Cancer

Abstract

In the past, patients with advanced or metastatic gastric or gastroesophageal junction cancer have had few treatment options and generally poor survival rates. The human epidermal growth factor receptor 2 (HER2) has been identified as a potential therapeutic target because of its overexpression or gene amplification in 6% to 35% of gastric or gastroesophageal junction cancers, although the methods of assessment and prognostic value of HER2 have been subject to debate. The phase III Trastuzumab for Gastric Cancer (ToGA) trial showed that adding the HER2-targeted humanized monoclonal antibody trastuzumab to chemotherapy significantly improves survival without negatively impacting quality of life in patients with advanced gastric or gastroesophageal junction cancer. As a result, trastuzumab is now the sole HER2-targeted therapy approved in several countries for this indication. The ToGA trial also demonstrated that patients who expressed higher levels of HER2 (determined by immunohistochemical screening) received the greatest benefit from trastuzumab therapy. This finding underlines the importance of accurate HER2 testing. Because of the unique characteristics of gastric cancer, a new gastric cancer-specific scoring system for HER2 expression was proposed during the ToGA trial. The aim of this review is to inform the gastroenterologist of the potential role of HER2-targeted therapy, to discuss the importance of accurate and reliable HER2 testing, and to discuss ongoing studies with HER2-targeted therapies that may have an impact on the future treatment of HER2-positive gastric cancer.