Ramucirumab/Paclitaxel as Second-line Treatment in Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma With Integrative Genomic Analysis

Vascular endothelial growth factor is expressed in gastric cancer, and expression has been associated with more aggressive clinical disease. Vascular endothelial growth factor expression has been noted in 51% of gastric cancer specimens in one series (versus no expression in normal epithelium or superficial gastritis). Vascular endothelial growth factor expression in resected gastric cancer is associated with tumor recurrence and shorter survival. Maeda et al. studied 95 gastric cancer patients following resection with curative intent, and noted a significantly shorter survival in 34 patients whose tumor endothelium expressed VEGF (as detected via immunohistochemistry) versus 61 patients without endothelial VEGF expression (p\533 pg/mL versus a 30-month survival rate \>35% for 34 patients with VEGF levels below this threshold (p\<0.0001, log-rank test). Recently, Jüttner and colleagues noted reduced survival following R0 resection in gastric cancer patients whose tumors expressed VEGF-C or VEGF-D, with the most robust association between expression and reduced survival for patients whose tumors expressed both VEGF-C and VEGF-D. Investigational inhibition of VEGF Receptor 2 in gastric cancer xenografts (TMK-1 cell line) is associated with reduced tumor growth. DC101 therapy in this model is associated with significant reductions in tumor vascularity (as measured by CD-31 expression) and increases in endothelial and tumor apoptosis. The results of the REGARD and RAINBOW studies are consistent with the i