Predictive Roles of HER2 Gene Amplification and Neutrophil-to-Lymphocyte Ratio on Survival in HER2-Positive Advanced Gastric Cancer Treated With Trastuzumab-Based Chemotherapy

Objectives: Trastuzumab is used as an agent against human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). The aim of this study was to determine how HER2 gene amplification and neutrophil-to-lymphocyte ratio (NLR) could predict long-term survival in AGC patients that underwent trastuzumab-based chemotherapy. Methods: We retrospectively reviewed medical records of 112 patients between 28 and 91 years old (median of 66 y) with AGC treated with first-line trastuzumab-based chemotherapy. The level of HER2 gene amplification was determined by the HER2/centromere enumerator probe 17 (CEP17) ratio and HER2 gene copy number (GCN). NLR was calculated as the neutrophil count divided by the lymphocyte counts. Results: Median HER2/CEP17 ratio, HER2 GCN, and NLR values were 2.85, 7.1, and 2.81, respectively. Objective response rate in both high HER2/CEP17 ratio (59.4% vs. 28.1%, P=0.012) and HER2 GCN groups (62.1% vs. 33.3%, P=0.032) was higher than that of each group. High NLR correlated with significantly worse median overall survival (OS) (median OS, 8.2 vs. 18.9 mo, P=0.002) and progression free survival (PFS) (median PFS: 5.1 vs. 8.0 mo, P=0.005). However, median OS and PFS were not significantly different according to HER2/CEP17 ratio or HER2 GCN. In the multivariate analysis, high NLR, Eastern Cooperative Group performance status, and poorly differentiated/signet ring cell type were independent factors for OS. Conclusions: NLR was a significant predictor of long-term survival in AGC patients treated with first-line trastuzumab-based chemotherapy. Future validation of prospective trials with larger patient populations will be needed.