J Cancer 2017; 8(10):1865-1871. doi:10.7150/jca.19867

Research Paper

The comparison of EGFR-TKI failure modes and subsequent management between exon 19 deletion and exon 21 L858R mutation in advanced non-small-cell lung cancer

Yaxiong Zhang1,#, Gang Chen1,#, Xi Chen1,#, Wenfeng Fang1, Fei Gao1, Yunpeng Yang1, Yuanyuan Zhao1, Yuxiang Ma1, Shaodong Hong1, Zhonghan Zhang1, Siyu Miao2, Manli Wu2, Xiaodan Huang2, Youli Luo3, Cong Zhou3, Run Gong3, Yan Huang1, Likun Chen1, Ningning Zhou1, Hongyun Zhao1, Li Zhang1,✉

1. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China;
2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;
3. The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, China;
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Zhang Y, Chen G, Chen X, Fang W, Gao F, Yang Y, Zhao Y, Ma Y, Hong S, Zhang Z, Miao S, Wu M, Huang X, Luo Y, Zhou C, Gong R, Huang Y, Chen L, Zhou N, Zhao H, Zhang L. The comparison of EGFR-TKI failure modes and subsequent management between exon 19 deletion and exon 21 L858R mutation in advanced non-small-cell lung cancer. J Cancer 2017; 8(10):1865-1871. doi:10.7150/jca.19867. Available from http://www.jcancer.org/v08p1865.htm

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Background: Advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion (19 Del) and exon 21 L858R mutation (L858R) might be distinct diseases. Therefore, it is necessary to take EGFR mutation subgroups into consideration for making choices of subsequent treatment after tyrosine kinase inhibitors (TKIs) failure.

Patients and methods: 174 patients who developed to EGFR-TKI failure were categorized into three cohorts of dramatic progression, gradual progression and local progression. Chi-square was used to compare the distribution of failure modes between 19 Del and L858R. Kaplan-Meier method and Cox Regression were performed for analyses of survival in different subsequent treatments.

Results: The distribution of EGFR-TKI failure modes showed no significant difference between 19 Del and L858R. Patients in gradual progression had a longer progression-free survival (PFS) and overall survival (OS) compared with other failure modes in whole population, 19 Del cohort and L858R cohort. 19 Del patients with dramatic progression would obtain survival benefit from chemotherapy, while those with gradual progression got no survival benefit neither from chemotherapy nor previous TKI continuation. However, patients with dramatic or gradual progression would benefit from previous TKI continuation in L858R cohort.

Conclusion: For advanced EGFR-positive NSCLC patients with acquired resistance to EGFR-TKI, subsequent treatment should be personalized according to EGFR-TKI failure modes & EGFR mutation subtypes.

Keywords: NSCLC, EGFR-TKI, 19 Del, L858R, clinical failure mode, subsequent treatment