Association of immune-related genes to neutrophil-lymphocyte ratio (NLR) with survival of cetuximab treatment for metastatic colorectal cancer (mCRC): JACCRO CC-05/06AR.

Abstract

11613 Background: The antitumor activity of cetuximab (cet) may be affected by extracellular immune mechanisms. We have reported that immune-related genes are associated with survival in mCRC patients (pts) treated with cet (ASCO 2016 abstract#11591). NLR reflects cancer-related inflammation and is a validated prognostic maker in many types of cancers; however, it is not currently used for treatment decision-making. The association between NLR and clinical outcome of cet treatment for mCRC is unknown, and which genes are affecting the NLR remain to be identified. Methods: We enrolled 77 pts (57% males and 15% right-colon cancer) with KRAS exon 2 wild-type from 2 phase II trials (JACCRO CC-05 or CC-06) of 1st-line therapy with FOLFOX or SOX plus cet. All patients’ tissues were measured for expression levels of 354 immune-related genes by HTG EdgeSeq Oncology Biomarker Panel using next generation sequencing for quantitative analysis of targeted RNAs. The association between the NLR and clinical outcome was evaluated using Spearman’s rank correlation coefficient. In addition, the two-sample t-test was performed to investigate which genes had significantly different expression level between NLR-low and high groups in top 100 genes associated with survival among all measured genes. Results: Seventy-one of 77 pts were available for NLR data. The NLR was associated with progression-free survival (PFS) and overall survival (OS) (r = 0.24; p= 0.04, r = 0.29; p= 0.01, respectively). When stratified by median value of NLR, the Kaplan-Meier curve of NLR-low (n = 36) vs. high (n = 35) had a significant difference in both PFS (median 11.8 vs. 9.1 m, p= 0.036) and OS (median 42.8 vs. 26.7 m, p= 0.029). The two-sample t-test revealed that LYZ, TYMP, and CD68 genes expressed significantly differently between NLR-low and high groups (t-test p-value < 0.005, FDR p-value < 0.150). Conclusions: NLR is significantly associated with survival of 1st-line cet treatment for mCRC. Genes encoding for activities on tissue macrophages and endothelial cells may affect the level of NLR associated with outcome of cet combination chemotherapy. Clinical trial information: UMIN000010635.