HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study

Abstract

PURPOSE Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2-positive (HER21) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC. METHODS Patients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, HER2 gene expression was assessed using qPCR. RESULTS Five hundred forty-eight patients were enrolled, and 77 had HER21 mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER21 mGC (central HER21/local HER21) lived significantly longer as compared with patients who received trastuzumab for local HER21 but central HER22 mGC (20.5 months, n = 60 v 10.9 months, n=65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; P