Clinical significance of MET amplification in metastatic or locally advanced gastric cancer treated with first-line fluoropyrimidine and platinum (FP) combination chemotherapy.

Abstract

69 Background: Amplification of the MET proto-oncogene has been reported in a subset of gastric cancer (GC). However, clinical information of MET amplified GC is limited, especially in the metastatic setting. We investigated the clinical significance of MET amplification in GC patients treated with palliative chemotherapy. Methods: MET amplification was analyzed in formalin-fixed, paraffin-embedded GC tissues by a quantitative PCR-based copy number assay, using advanced GC cohorts between 2008 and 2014 in Asan Medical Center (AMC), Seoul, Korea. A total of 327 patients with tumor portion ≥ 70% were analyzed for clinical features and among them, 260 patients treated with first-line FP were analyzed for survival. MET amplification was defined as > 5 copy number. Results: Twenty one out of 327 patients (6.4%) were classified as harboring MET amplification. Clinical characteristics were compared between patients with or without MET amplification (AMP vs. no AMP group). The AMP group was related with ECOG performance status ≥ 2 (33.3% vs. 10.5% p = 0.007), peritoneal metastasis (76.2% vs. 46.2%, p = 0.008) and poor risk category (47.6% vs. 14.2%, p = 0.001) by AMC prognostic model (Koo et al. Cancer Chemother Pharmacol 2011, 68:913-921). A total of 174 patients had measurable lesions from 260 patients treated with FP and 80 patients (51.4%) obtained objective responses. There were no significant differences in response rate between two groups (61.5% vs. 52.2%, p = 0.518). With a median follow-up of 27.8 months (range, 8.2-68.5), median overall survival (OS) and progression-free survival (PFS) were 12.7 and 5.8 months, respectively. In univariate analysis, neither PFS nor OS was different between two groups (hazard ratio [HR] = 0.677, 95% confidence interval [CI] 0.347-1.322, p = 0.254 for PFS; HR = 0.676, 95% CI 0.347-1.318, p = 0.251 for OS). Conclusions: In advanced GC, MET amplification was associated with poor performance status, peritoneal metastasis, and poor risk category. However, MET amplification was not an independent prognostic predictor in patients with metastatic or locally advanced GC treated with palliative FP chemotherapy.