HER2 directed therapy for gastric/esophageal cancers

Abstract

The majority of patients with esophagogastric cancer present with advanced disease, which is incurable. Systemic chemotherapy can lead to a decrease in cancer-related symptoms and prolongs survival. However, even with treatment, the prognosis remains poor; most patients with advanced disease have a median overall survival less than one year. Molecularly targeted therapies, such as those targeting human epidermal growth factor receptor 2 (HER2), are anticipated to improve the current status of systemic treatment beyond conventional cytotoxic therapy. Trastuzumab in combination with chemotherapy in patients is the first molecular agent in metastatic HER2 positive gastric and gastroesophageal adenocarcinomas to result in improvements in response rates, time to progression and survival. Trastuzumab is now being investigated in the neoadjuvant and adjuvant setting. Unfortunately, as with breast cancer, many esophagogastric patients will develop resistance to trastuzumab. Several promising therapies are currently under investigation as monotherapy and in combination with chemotherapy in the first and second line setting.