Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, PR China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, PR China.
Lung Cancer. 2018 Nov;125:22-28. doi: 10.1016/j.lungcan.2018.08.025. Epub 2018 Aug 31.
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.
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.
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).
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.
尽管表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）是 EGFR 突变非小细胞肺癌（NSCLC）患者的标准治疗方法，但个体内的反应存在差异。本研究旨在探讨治疗前和治疗 1 个月时血清中几种细胞因子的水平及其在 TKI 治疗过程中的动态变化是否可用于预测 EGFR-TKIs 的疗效。
采用酶联免疫吸附试验和 U-plex 生物标志物组检测试剂盒检测 EGFR 突变 NSCLC 患者一线接受 EGFR-TKIs 治疗前和治疗 1 个月后的血清肝细胞生长因子（HGF）、白细胞介素-10（IL-10）、白细胞介素-6（IL-6）、血管内皮生长因子（VEGF）、干扰素-γ（IFN-γ）和单核细胞趋化蛋白-1（MCP-1）的水平。
基线时血清 IL-6 水平较低的患者客观缓解率（ORR）高于血清 IL-6 水平较高的患者（74.2% vs. 42.9%，p=0.014）。基线时血清 IL-6 水平较低的患者无进展生存期（PFS）明显延长（19.57 个月 vs. 13.73 个月，p=0.003），治疗后血清 VEGF 和 HGF 水平降低的患者 PFS 也明显延长（20.30 个月 vs. 14.33 个月，p=0.009；22.77 个月 vs. 14.33 个月，p=0.002）。多变量分析显示，基线时血清 IL-6 水平较低与 PFS 延长显著相关（HR=0.469，p=0.022）和 OS 延长显著相关（HR=0.181，p=0.004）。治疗后血清 VEGF 和 HGF 水平降低与 PFS 延长显著相关（HR=0.447，p=0.017；HR=0.365，p=0.003）。治疗前血清 VEGF 水平较低与 OS 延长显著相关（HR=0.277，p=0.018）。
本研究表明，HGF、IL-6 和 VEGF 血清水平及其在 TKI 治疗过程中的动态变化可用于预测 EGFR-TKIs 治疗 EGFR 突变 NSCLC 患者的疗效。
