Research Papers:

The role of T790M mutation in EGFR-TKI re-challenge for patients with EGFR-mutant advanced lung adenocarcinoma

Qiuyi Zhang, Ee Ke, Feiyu Niu, Wei Deng, Zhihong Chen, Chongrui Xu, Xuchao Zhang, Ning Zhao, Jian Su, Jinji Yang, Honghong Yan, Yilong Wu and Qing Zhou _

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Oncotarget. 2017; 8:4994-5002. https://doi.org/10.18632/oncotarget.14007

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Qiuyi Zhang1, Ee Ke1, Feiyu Niu1, Wei Deng1, Zhihong Chen1, Chongrui Xu1, Xuchao Zhang1, Ning Zhao1, Jian Su1, Jinji Yang1, Honghong Yan1, Yilong Wu1, Qing Zhou1

1Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, PR China

Correspondence to:

Qing Zhou, email: [email protected]

Yi-Long Wu, email: [email protected]

Keywords: adenocarcinoma, TKI-free interval, T790M mutation, re-challenge, resistance

Received: April 16, 2016     Accepted: December 05, 2016     Published: December 17, 2016


Epidermal growth factor receptor (EGFR) T790M mutation has shown to be associated with the clinical outcomes of patients after initial EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy in EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, its predictive role in EGFR-TKI re-challenge remains unknown. The present study was aimed to explore the correlation between T790M mutation and any benefits from EGFR-TKI re-challenge. We retrospectively reviewed 922 consecutive patients with EGFR-mutant non-small cell lung cancer (NSCLC) patients administered with gefitinib/erlotinib at Guangdong General Hospital. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were analyzed respectively. In total, 66 EGFR-mutant patients with stage IV adenocarcinoma were eligible, of whom 51 underwent re-biopsy upon initial progression. Among them, 18 (35.3%) harbored T790M mutation. No statistical significant differences were seen between T790M-positive and T790M-negative patients in PFS, OS, ORR or DCR. The median PFS, median OS, ORR, and DCR of the overall 66 patients were 2.0 months, 6.8 months, 6.1% and 39.4%, respectively. Good performance status (PS) was found to be independent favorable prognostic factor and long TKI-free interval to be associated with superior PFS. In conclusion, T790M mutation might not predict the clinical outcomes in first-generation EGFR-TKI re-challenge. Based on the poor efficacy from our data, re-challenge of first-generation EGFR-TKIs could not be recommended routinely, but for those with good PS and long TKI-free interval, it might be an alternative option.

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