Gastric cancer is the fifth most common cancer form worldwide and the third most deadly cancer form. Gastric cancer is a disease in which cancer cells form in the lining of the stomach. Almost all gastric cancers are adenocarcinomas (i.e. a cancer that begins in glandular tissue) and some gastric cancers over-express the molecule HER2. However, 80 percent or more of gastric cancer patients are HER2-negative (i.e. having no over-expression of the HER2 molecule), meaning that they are ineligible for therapies targeting the HER2 molecule. Gastric cancer is often in an advanced stage (i.e. un-resectable and/or metastatic) when it is diagnosed. At this stage it often can be treated, but rarely cured. In Western countries, 80-90 percent of gastric cancer patients are diagnosed at an advanced stage and/or have disease relapse within five years. For patients with gastric cancer, the five-year survival rate is around 20 percent and the median survival of patients with advanced disease receiving combination chemotherapy is less than one year. It is worth noting that there are substantial geographic variations in gastric cancer incidence and survival rates. The incidence in Japan is roughly the same as the incidence in the United States and the EU/EEA combined, and the five-year survival in Japan is around 60 percent.
TYPICAL TREATMENT OF ADVANCED GASTRIC CANCER
The current backbone of first-line treatment of advanced gastric cancer is chemotherapy, either as doublet or triplet combinations. A widely used first line chemotherapeutic regime is fluorouracil (5-FU) or capecitabine in combination with a platinum agent (potentially with the addition of epirubicin or a taxane). 5-FU is typically infused over 48 hours whereas capecitabine is an oral prodrug formulation (i.e. an inactive drug that is designed to be converted into the active compound in the body) that is converted in the body to 5-FU and considered equally efficacious as intravenous 5-FU. Irinotecan, which is usually infused over 30-90 minutes, is not regulatorily approved for treatment of gastric cancer in the United States and the EU/EEA, but it is used off-label and included in recognized clinical guidelines in monotherapeutic or combination treatment regimens for advanced gastric cancer. According to these guidelines, 5-FU in combination with irinotecan might be considered in the first line setting, and in the second line setting irinotecan may be used as an alternative to a taxane or the anti-VEGFR2 antibody ramucirumab.
References: Clinical Colorectal Cancer 2015; 14(4): 239-50. World J Gastroenterol 2015; 21(41):11621-11635. Globocan 2012 and WHO Cancer Fact Sheets. Clinical guidelines from ESMO, ASCO and NCCN.