Incorporating targeted therapy into oesophagogastric cancer management


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David Cunningham
Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom

Abstract

Oesophageal and gastric cancers are the 2nd and 6th most common cause of cancer-related death worldwide, representing a significant global health problem.  Multimodality therapy has improved localized disease outcomes, but survival rates remain poor.  In advanced disease, chemotherapy improves survival, but median survival remains less than one year due to either primary or acquired chemotherapy resistance.  The first targeted agent to demonstrate survival benefit in advanced oesophagogastric cancer is the anti-HER-2 monoclonal antibody trastuzumab which is now licensed in combination with doublet chemotherapy for patients with HER-2 positive disease.  Disappointingly, the addition of the anti-VEGF monoclonal antibody, bevacizumab, does not significantly prolong overall survival in advanced disease but is being evaluated in the perioperative treatment of localised disease.  Other agents currently undergoing phase III evaluation in advanced oesophagogastric cancer include the anti-EGFR monoclonal antibodies cetuximab and panitumumab, the anti-EGFR tyrosine kinase inhibitor (TKI), gefitinib, the dual EGFR/HER-2 tyrosine TKI lapatinib, anti-VEGFR2 monoclonal antibody ramucirumab and the mTOR inhibitor, everolimus.  These studies have been designed with translational sub-studies, attempting to define a sub-set of patients who gain benefit from these high cost novel agents.  Further targets of interest in oesophagogastric cancer will be discussed.