High EGFR copy number predicts benefits from tyrosine kinase inhibitor treatment for non-small cell lung cancer patients with wild-type EGFR

Journal of Translational Medicine

Jian-Yong Shao⁵  Wei-Min Zhang³  Li Zhang²  Li-Xia Huang¹  Jian-Guang Lin³  Cong Xue²  Xu Zhang⁴  Xiao Zhang⁴  Yan-Bin Zhou¹  Qiong Shao⁴  Sha Fu⁶  Fang Wang⁴ 

[1] Department of Internal Medicine and Pulmonary Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China;Department of Medicine Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;Department of Oncology, General Hospital of Guangzhou Military Command, Guangzhou, China;Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, 651 Dongfeng Rd East, Guangzhou 510060, China;Lung Cancer Institute, Sun Yat-sen University, Guangzhou, China;State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

关键词: Lung cancer;    Copy number;    Mutation;    EGFR;   

Others  :  827803
DOI  :  10.1186/1479-5876-11-90

 received in 2012-12-16, accepted in 2013-03-23,  发布年份 2013

【 摘 要 】

Background

This study was designed to determine whether advanced non-small-cell lung cancer (NSCLC) patients with high copy number of epidermal growth factor receptor (EGFR) can benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs).

Methods

EGFR gene copy number was assessed by fluorescence in situ hybridization (FISH) and EGFR mutations was tested using Luminex xTAG technology in 502 TKI-treated NSCLC patients. The association between both biomarkers and clinical benefit from EGFR-TKI were analyzed.

Results

EGFR FISH + and EGFR mutations were significantly associated with higher response rates (37.2% and 43.7%, respectively), superior progression-free survival (PFS) (FISH+, 11.2 months; hazard ratio [HR], 0.51; 95% CI, 0.42 to 0.62; p < 0.001; mutation+, 11.7 months; HR, 0.37; 95% CI, 0.31 to 0.45; p < 0.001) and overall survival (OS) (FISH+, 30.2 months; HR, 0.51; 95% CI, 0.40 to 0.65; p < 0.001; mutation+, 30.2 months; HR, 0.45; 95% CI, 0.36 to 0.58; p < 0.001). In patients with wild-type EGFR, EGFR FISH + correlated with longer PFS than EGFR FISH- status (4.4 months vs. 2.0 months; HR, 0.56; 95% CI, 0.41 to 0.75; p < 0.001), so did amplification (5.0 months vs. 2.0 months; HR, 0.43; 95% CI, 0.24 to 0.76; p = 0.003). However, FISH + had no association with improved PFS in EGFR-mutated patients (HR, 0.77; 95% CI, 0.57 to 1.03; p = 0.076).

Conclusions

A combined analysis of EGFR FISH and mutation is an effective predictor of EGFR-TKI therapy. Specifically, a high EGFR copy number may predict benefit from TKIs treatment for NSCLC patients with wild-type EGFR.

【 授权许可】

   
2013 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 3.

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