表皮生长因子受体表达在筛选晚期非小细胞肺癌患者接受厄洛替尼治疗中的临床应用价值

Clinical utility of epidermal growth factor receptor expression for selecting patients with advanced non-small cell lung cancer for treatment with erlotinib.

作者信息

Clark Gary M, Zborowski Denni M, Culbertson Jennifer L, Whitehead Marlo, Savoie Michelle, Seymour Lesley, Shepherd Frances A

机构信息

OSI Pharmaceuticals, Inc., Boulder, CO 80301, USA.

出版信息

J Thorac Oncol. 2006 Oct;1(8):837-46.

PMID:17409968

Abstract

INTRODUCTION

Erlotinib (Tarceva) has demonstrated a survival benefit in unselected patients with advanced non-small cell lung cancer (NSCLC) after failure of chemotherapy. Because not all patients benefit from erlotinib, epidermal growth factor receptor (EGFR) protein expression may provide a basis for selecting patients for treatment with this EGFR inhibitor.

METHODS

Tumor samples from patients who participated in National Institute of Canada Clinical Trials Group Study BR.21 were assayed by immunohistochemistry using Dako EGFR pharmDx kits. EGFR expression was scored as proportion of tumor cells with membrane staining, staining intensity, and combined proportion and intensity scores. All possible cutpoints were examined to determine whether EGFR protein expression status by immunohistochemistry might be useful for predicting patient survival.

RESULTS

Three hundred twenty-five patients had evaluable assay results. The prognostic significance of EGFR protein expression was modest. Patients with EGFR-positive tumors who received placebo after failure of chemotherapy had slightly worse survival than patients with EGFR-negative tumors; however, the differences were not statistically significant for any cutpoint for any of the three measures of EGFR protein expression. The treatment benefits from erlotinib relative to placebo were greater for EGFR-positive patients compared with EGFR-negative patients, but they were not significantly different for any cutoff used to define EGFR positivity. Use of very high cutpoints to define patients with EGFR-rich tumors that might be especially sensitive to treatment with erlotinib cannot be supported by these data.

CONCLUSIONS

Selection or exclusion of NSCLC patients for erlotinib therapy after failure of standard therapy for advanced or metastatic disease should not be based solely on EGFR protein expression as determined by immunohistochemistry.

摘要

引言

厄洛替尼（特罗凯）已证实在化疗失败后的晚期非小细胞肺癌（NSCLC）未选择患者中具有生存获益。由于并非所有患者都能从厄洛替尼中获益，表皮生长因子受体（EGFR）蛋白表达可能为选择使用这种EGFR抑制剂治疗的患者提供依据。

方法

使用Dako EGFR pharmDx试剂盒通过免疫组织化学对参与加拿大国家临床试验组研究BR.21的患者的肿瘤样本进行检测。EGFR表达根据具有膜染色的肿瘤细胞比例、染色强度以及比例和强度综合评分进行评分。检查所有可能的切点以确定免疫组织化学检测的EGFR蛋白表达状态是否有助于预测患者生存。

结果

325例患者有可评估的检测结果。EGFR蛋白表达的预后意义不大。化疗失败后接受安慰剂的EGFR阳性肿瘤患者的生存略差于EGFR阴性肿瘤患者；然而，对于EGFR蛋白表达的三种测量方法中的任何一种，任何切点的差异均无统计学意义。与EGFR阴性患者相比，EGFR阳性患者从厄洛替尼相对于安慰剂的治疗中获益更大，但对于用于定义EGFR阳性的任何临界值，差异均无统计学意义。这些数据不支持使用非常高的切点来定义可能对厄洛替尼治疗特别敏感的富含EGFR肿瘤的患者。