Impact of serum vascular endothelial growth factor and interleukin-6 on treatment response to epidermal growth factor receptor tyrosine kinase inhibitors in patients with non-small-cell lung cancer.

Abstract

BACKGROUND:

Although EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment for patients with EGFR-mutant non-small-cell lung cancer (NSCLC), responses vary within individuals. The current study aimed to investigate whether serum levels of several cytokines and their dynamic changes during TKI treatment could be used to predict the efficacy of EGFR-TKIs.

MATERIALS AND METHODS:

Pre-treatment and one-month post-treatment serum levels of hepatocyte growth factor (HGF), interleukin-10 (IL-10), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ) and monocyte chemotactic protein-1 (MCP-1) were measured using enzyme-linked immunosorbent assay and U-plex biomarker group assays in patients with EGFR-mutant NSCLC received first-line EGFR-TKIs.

RESULTS:

Patients who had lower baseline serum levels of IL-6 had better object response rate (ORR) than those with high levels (74.2% vs 42.9%, p = 0.014). PFS was significantly longer in patients with low baseline level of IL-6 (19.57 vs. 13.73 months, p = 0.003) and in those with reduced serum VEGF and HGF levels after treatment (20.30 vs. 14.33 months, p = 0.009; 22.77 vs. 14.33 months, p =  0.002; respectively). Multivariate analyses showed that lower baseline serum IL-6 level was significantly associated with longer PFS (HR = 0.469, p = 0.022) and OS (HR = 0.181, p = 0.004). Reduction of serum VEGF and HGF levels after treatment was associated with significantly longer PFS (HR = 0.447, p = 0.017; HR = 0.365, p = 0.003; respectively). Lower pre-treatment serum VEGF level was associated with dramatically longer OS (HR = 0.277, p = 0.018).

CONCLUSIONS:

Our study suggested that serum levels of HGF, IL-6 and VEGF and its dynamic change during TKI treatment could be used to predict the efficacy of EGFR-TKIs treatment in patients with EGFR-mutant NSCLC.

• Authors: Yijun Jia, Xuefei Li, Chao Zhao, Tao Jiang, Sha Zhao, Limin Zhang, Xiaozhen Liu, Jinpeng Shi, Meng Qiao, Jiawei Luo, Sangtian Liu, Ruoshuang Han, Xiaoxia Chen, Caicun Zhou
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 125 Pg. 22-28 (11 2018) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 30429024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Chemokine CCL2
• IL6 protein, human
• Interleukin-6
• Protein Kinase Inhibitors
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Interleukin-10
• Hepatocyte Growth Factor
• Interferon-gamma
• EGFR protein, human
• ErbB Receptors

Topics

• Adult
• Aged, 80 and over
• Biomarkers, Tumor (blood)
• Carcinoma, Non-Small-Cell Lung (blood, drug therapy)
• Chemokine CCL2 (blood)
• ErbB Receptors (blood)
• Female
• Hepatocyte Growth Factor (blood)
• Humans
• Interferon-gamma (blood)
• Interleukin-10 (blood)
• Interleukin-6 (blood)
• Lung Neoplasms (blood, drug therapy)
• Male
• Middle Aged
• Mutation (genetics)
• Protein Kinase Inhibitors (therapeutic use)
• Vascular Endothelial Growth Factor A (blood)