Qiu Miaozhen¹, Ruihua Xu², Yixin Zhou², Deshen Wang², Dongsheng Zhang², Fenghua Wang², Yuhong Li², Jacqueline Huang³, Hui Zhou³, En-tzu Tang⁴, Zhiqiang Du⁵, Yanni Zhang⁵

¹Sun Yat-Sen University Cancer Center, Department of Medical Oncology, ²Department of Medical Oncology, Sun Yat-Sen University Cancer Center, ³Medical Department, Amgen Inc., Shanghai, China, ⁴Biostatistical Science, Amgen Inc., ⁵Translational Science, Amgen Inc., Shanghai, China

Objective:Gastric cancer is a disease with high unmet medical needs in China. MET and its ligand, hepatocyte growth factor, are potential targets in G/GEJ cancer. This study evaluated overall survival (OS) according to tumor MET expression, MET gene amplification, and the association between MET and HER2 status in Chinese patients with advanced G/GEJ cancer. Method:Baseline tumor biopsy samples (formalin-fixed, paraffin-embedded primary tumor) from patients with stage IV unresectable G/GEJ cancer, archived at Sun Yat-Sen University Cancer Center, were assessed for MET and HER2protein levels and MET and HER2 gene amplification by IHC and FISH, respectively. MET-positive: membrane protein staining in ≥25% or ≥50% of tumor cells. HER2-positive: IHC 2+ and a confirmatory HER2 FISH-positive result (HER2: centromere 17 ratio ≥2.0), or IHC 3+. MET-amplified: MET: centromere 7 ratio>2.0.We evaluated associations between Kaplan-Meier OS and MET status (log-rank test), MET expression and MET gene amplification, and MET and HER2 status (Fisher exact test). Result: Of 289 eligible patients, 271 had evaluable IHC samples, and MET-positive rates were 42.1% and 25.1% by 25% and 50% cutoffs, respectively. Median OS by different levels of MET-positive expression is shown in the Table. Of 183 patients with evaluable FISH samples, 8 (4.4%) were MET-amplified. In 171 patients with IHC and FISH data, MET-positive expression by 25% and 50% cutoffs was associated with MET amplification (P). In 145 patients with METIHC, FISH, and HER2 data, the HER2-positive rate was 13.8%. Of patients who were MET-positive by 25% and 50% cutoffs, 8/48 (16.7%) and 4/29 (13.8%), respectively, were also HER2-positive. Additionally, 1/8 (12.5%) MET-amplified patients was HER2-positive. Conclusion: MET-positive status was associated with shorter OS in this population of Chinese patients with advanced G/GEJ cancer. MET high expression or MET amplification was not associated with HER2 expression. Patients evaluable for IHC MET-positive MET-negative P value 25% cut off n 114 157 OS, mo* 10.9 16.0 0.054 50% cut off n 68 203 OS, mo* 8.3 15.5.

Key Words: MET  gastric or gastroesophageal junction cancer