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

Abstract

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.

The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy

“…All the covariates used are known, and feature in other models for prognosis in HER2-negative AGA. 13 The contribution of NLR is known in AGA 29 and other advanced malignancies, reflecting the presence of a systemic proinflammatory state. 30 , 31 It should be noted that the effect on survival-based endpoints is non-linear, with a threshold between 6 and 8, beyond which successive increases are not associated with worse prognosis.…”