Poor efficacy response to trastuzumab therapy in advanced gastric cancer with homogeneous HER2 positive and non-intestinal type

INTRODUCTION: Factors affecting trastuzumab efficacy in advanced gastric cancer (GC) are largely unknown. Heterogeneity is a notable feature of HER2 in GC. Whether the heterogeneity influences trastuzumab efficacy is still unknown. RESULTS: The HER2(homogeneous) group and HER2(heterogeneous) group showed no statistical difference in RR (46.4% vs 55.0%, P = 0.558), PFS (5.80 vs 6.30 months, P = 0.804) and OS (16.00 vs 16.00 months, P = 0.787). The Lauren(intestinal) group and Lauren(non-intestinal) group demonstrated no discrepancy in PFS (6.00 vs 6.00 months, P = 0.912) and OS (16.50 vs 14.00 months, P = 0.227). However, by combining HER2 heterogeneity and Lauren classification, PFS and OS of HER2(homogeneous)/Lauren(non-intestinal) subgroup was the shortest among the 4 subgroups (P = 0.012 and P = 0.037), which was much shorter than the other patients (PFS:3.00 vs 6.30 months, P = 0.003; OS: 4.50 vs 16.50 months, P = 0.004). Univariate and multivariate analysis showed that HER2 heterogeneity combined with Lauren classification was an independent prognostic factor in both PFS (P = 0.031 and P = 0.002) and OS (P = 0.039 and P = 0.013). MATERIALS AND METHODS: 48 patients with HER2 positive advanced GCs accepting trastuzumab treatment were retrospectively analyzed. Based on HER2 heterogeneity, the patients were divided into a HER2(homogeneous) group and a HER2(heterogeneous) group. Response rate (RR), progression free survival (PFS), and overall survival (OS) were compared. Main clinicopathological factors including Lauren classification were subjected to subgroup analysis. CONCLUSIONS: HER2 heterogeneity alone may not correlate with trastuzumab efficacy in HER2 positive advanced GCs. HER2 heterogeneity combined with Lauren classification may help to identify a subgroup with poor response to trastuzumab which is homogeneous HER2 positive and non-intestinal type.