表皮生长因子受体 (EGFR) 突变的非小细胞肺癌患者接受 EGFR 酪氨酸激酶抑制剂治疗的不同临床结局：无应答者与应答者。

Distinct clinical outcomes of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors: non-responders versus responders.

机构信息

Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.

Division of Hematology and Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

出版信息

PLoS One. 2013 Dec 23;8(12):e83266. doi: 10.1371/journal.pone.0083266. eCollection 2013.

DOI:10.1371/journal.pone.0083266

PMID:24376677

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3871587/

Abstract

INTRODUCTION

Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations. However, a subset of this population doesn't respond to EGFR-TKI treatment. Therefore, the present study aimed to elucidate survival outcome in NSCLC EGFR-mutant patients who were treated with EGFR TKIs.

METHODS

Among the 580 consecutive NSCLC patients who were treated at our facility between 2008 and 2012, a total of 124 treatment-naïve, advanced NSCLC, EGFR-mutant patients treated with EGFR TKIs were identified and grouped into non-responders and responders for analyses.

RESULTS

Of 124 patients, 104 (84%) responded to treatment, and 20 (16%) did not; and the overall median PFS was 9.0 months. Notably, the PFS, overall survival (OS) and survival rates were significantly unfavorable in non-responders (1.8 vs. 10.3 months, hazard ratio (HR) = 29.2, 95% confidence interval (CI), 13.48-63.26, P<0.0001; 9.4 vs. 17.3 months, HR = 2.74, 95% CI, 1.52-4.94, P = 0.0008; and 58% vs. 82% in 6, 37% vs. 60% in 12, and 19 vs. 40% at 24 months, respectively). In multivariate analysis, treatment efficacy strongly affected PFS and OS, independent of covariates (HR = 47.22, 95% CI, 17.88-124.73, P<0.001 and HR = 2.74, 95% CI, 1.43-5.24, P = 0.002, respectively). However, none of the covariates except of the presence of EGFR exon 19 deletion in the tumors was significantly associated with better treatment efficacy.

CONCLUSIONS

A subset of NSCLC EGFR-mutant patients displayed unfavorable survival despite EGFR TKI administration. This observation reinforces the urgent need for biomarkers effectively predicting the non-responders and for drug development overcoming primary resistance to EGFR TKIs. In addition, optimal therapeutic strategies to prolong the survival of non-responders need to be investigated.

摘要

简介

表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗与非小细胞肺癌（NSCLC）患者的无进展生存期（PFS）改善相关，这些患者携带 EGFR 突变。然而，该人群中的一部分对 EGFR-TKI 治疗没有反应。因此，本研究旨在阐明接受 EGFR TKI 治疗的 NSCLC EGFR 突变患者的生存结果。

方法

在 2008 年至 2012 年期间在我们机构治疗的 580 例连续 NSCLC 患者中，共确定了 124 例未经治疗的晚期 NSCLC、EGFR 突变患者接受 EGFR TKI 治疗，并分为无反应者和有反应者进行分析。

结果

124 例患者中，104 例（84%）有反应，20 例（16%）无反应；总体中位 PFS 为 9.0 个月。值得注意的是，无反应者的 PFS、总生存期（OS）和生存率明显较差（1.8 与 10.3 个月，风险比（HR）=29.2，95%置信区间（CI）13.48-63.26，P<0.0001；9.4 与 17.3 个月，HR=2.74，95%CI 1.52-4.94，P=0.0008；6 个月时分别为 58%和 82%，12 个月时分别为 37%和 60%，24 个月时分别为 19%和 40%）。多变量分析显示，治疗效果是影响 PFS 和 OS 的重要因素，不受协变量的影响（HR=47.22，95%CI 17.88-124.73，P<0.001 和 HR=2.74，95%CI 1.43-5.24，P=0.002）。然而，除肿瘤中存在 EGFR 外显子 19 缺失外，没有其他协变量与更好的治疗效果显著相关。