Abstract
ABSTRACT Aim: Gastric cancer accounts for >325,000 deaths in China annually. MET and its ligand hepatocyte growth factor are promising targets in G/GEJ cancer. This study evaluated overall survival (OS) by tumor MET expression and by treatment disposition in Chinese pts with advanced G/GEJ cancer. Methods: Baseline formalin-fixed, paraffin-embedded tumor samples from pts with stage IV unresectable G/GEJ cancer enrolled in clinical trials during 2008–2010 were assessed for MET protein levels and MET gene copy numbers by immunohistochemistry (IHC; Dako) and fluorescence in situ hybridization (FISH; Dako), respectively. MET-positive: membrane protein staining in ≥25% tumor cells. MET-amplified: MET:centromere ratio ≥2.0. We tested the association between Kaplan-Meier OS and MET status (log-rank test) and clinical parameters (Fisher's exact), and the association between MET expression and amplification (Fisher's exact). Results: 168 pts were eligible; 137 had evaluable IHC samples. OS by MET status is shown (Table). Of 113 pts with evaluable FISH samples, 8 were MET-amplified. MET expression and amplification were not associated with sex, primary tumor site, prior surgery, lung or liver metastases, or number of metastases. Lauren classification was associated with MET amplification (P=0.038) but not MET expression (P=0.446). In 95 pts with evaluable IHC and FISH samples, MET expression was associated with MET amplification (P Patients Evaluable for IHC MET-positive MET-negative P-valued Overall, n 53 84 – OS analysis, n 51 82 – Median OS, mo 12.3 10.9 0.799 First-line platinum-based,a n 35 47 – OS analysis, n 33 47 – Median OS, mo 11.3 11.8 0.367 First-line platinum-based only,b n 30 34 – OS analysis, n 28 34 – Median OS, mo 10.6 11.9 0.119 First-line taxane-based,a,c n 23 50 – OS analysis, n 23 48 – Median OS, mo 12.6 10.8 0.259 aIncludes platinum- and taxane-based triplet (n=18). bExcludes platinum- and taxane-based triplet (n=18). cIncludes paclitaxel alone (n=1). dLog-rank test. Conclusions: Tumor MET expression was not significantly associated with OS in this population of Chinese pts with advanced G/GEJ cancer. The study was limited by the small sample size and unbalanced treatment disposition between MET-positive and MET-negative pts. Prospective analysis of potential prognostic markers in Chinese pts with advanced G/GEJ cancer is needed. Disclosure: K.S. Oliner: employment by and stock ownership in Amgen Inc.; Y. Hei: employment by and stock ownership in Amgen Inc.; H. Zhou: employment by and stock ownership in Amgen Inc. All other authors have declared no conflicts of interest.
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