Research Papers:

Optimized selection of three major EGFR-TKIs in advanced EGFR-positive non-small cell lung cancer: a network meta-analysis

Yaxiong Zhang, Jin Sheng, Yunpeng Yang, Wenfeng Fang, Shiyang Kang, Yang He, Shaodong Hong, Jianhua Zhan, Yuanyuan Zhao, Cong Xue, Yuxiang Ma, Ting Zhou, Shuxiang Ma, Fangfang Gao, Tao Qin, Zhihuang Hu, Ying Tian, Xue Hou, Yan Huang, Ningning Zhou, Hongyun Zhao and Li Zhang _

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Oncotarget. 2016; 7:20093-20108. https://doi.org/10.18632/oncotarget.7713

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Yaxiong Zhang1,2,3,*, Jin Sheng1,2,3,*, Yunpeng Yang1,2,3,*, Wenfeng Fang1,2,3, Shiyang Kang2,3,4, Yang He5, Shaodong Hong1,2,3, Jianhua Zhan1,2,3, Yuanyuan Zhao1,2,3, Cong Xue1,2,3, Yuxiang Ma1,2,3, Ting Zhou1,2,3, Shuxiang Ma1,2,3, Fangfang Gao1,2,3, Tao Qin1,2,3, Zhihuang Hu1,2,3, Ying Tian1,2,3, Xue Hou1,2,3, Yan Huang1,2,3, Ningning Zhou1,2,3, Hongyun Zhao1,2,3, Li Zhang1,2,3

1Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2State Key Laboratory of Oncology in South China, Guangzhou, China

3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

4Department of Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou, China

5Lau Luen Hung Private Medical Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Li Zhang, e-mail: [email protected]

Keywords: EGFR-TKI, NSCLC, gefitinib, erlotinib, afatinib

Received: January 21, 2016     Accepted: February 18, 2016     Published: February 25, 2016


Background: To answer which epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the best choice for advanced non-small cell lung cancer (NSCLC) EGFR mutants.

Results: 16 phase III randomized trials involving 2962 advanced NSCLC EGFR mutants were enrolled. Multiple treatment comparisons showed different EGFR-TKIs shared equivalent curative effect in terms of all outcome measures among the overall, chemo-naïve and previously treated patients. Rank probabilities showed that erlotinib and afatinib had potentially better efficacy compared with gefitinib in both of the overall and chemo-naïve patients. Potentially survival benefit of erlotinib was also observed in previously treated patients compared with gefitinib. Additionally, EGFR-TKI showed numerically greater survival benefit in 19 Del compared with chemotherapy, while it was opposite in 21 L858R. Furthermore, afatinib, erlotinib and gefitinib had high, moderate and low risk of rash & diarrhea, respectively, while the occurrence of elevated liver transaminase was more common in gefitinib.

Methods: Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were extracted from included studies. Efficacy and toxicity of all included treatments were integrated by network meta-analyses.

Conclusion: Our study indicated a high efficacy-high toxicity pattern of afatinib, a high efficacy-moderate toxicity pattern of erlotinib and a medium efficacy-moderate toxicity pattern of gefitinib. Recommended EGFR-TKI should be suggested according to patients’ tolerability and therapeutic efficacy in clinical practice. Moreover, the treatment for advanced EGFR-positive NSCLC might be different between 19 Del and 21 L858R.

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