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Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs

Authors Liu Y, Sun L, Xiong Z, Sun X, Zhang S, Ma J, Han C

Received 24 January 2017

Accepted for publication 25 March 2017

Published 24 April 2017 Volume 2017:10 Pages 2267—2279


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Carlos E Vigil

Yang Liu, Li Sun, Zhi-Cheng Xiong, Xin Sun, Shu-Ling Zhang, Jie-Tao Ma, Cheng-Bo Han

Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China

Purpose: The purpose of this meta-analysis was to explore the influences of pretreatment de novo and posttreatment-acquired epidermal growth factor receptor (EGFR) T790M mutations in patients with advanced non-small cell lung cancer (NSCLC) who had received tyrosine kinase inhibitors (TKIs).
Methods: We searched PubMed, Embase, and the China National Knowledge Infrastructure database for eligible literature. Data were extracted to assess the hazard ratios (HRs) for progression-free survival (PFS), overall survival (OS), and post-progression survival (PPS) and the relative ratios (RRs) for objective response rate (ORR).
Results: This meta-analysis included 22 studies comprising 1,462 patients with NSCLC who harbored activating EGFR mutations and were treated with EGFR-TKIs. Compared to pretreatment T790M mutation-negative NSCLC, pretreatment T790M mutation-positive NSCLC was associated with decreased PFS (HR 2.23, P<0.001) and OS (HR 1.55, P=0.003). A trend toward significance of worsening ORR (RR 0.86, P=0.051) was evident. The acquired T790M mutation was correlated with improved PFS (HR 0.75, P=0.006) and PPS (HR 0.57, P<0.001), compared to patients without the T790M mutation who progressed after EGFR-TKI treatment. There were no significant differences in OS or ORR between patients with acquired T790M mutation-positive and T790M mutation-negative NSCLC. However, in the tumor tissue rebiopsy subgroup, patients with acquired T790M mutation had improved OS (HR 0.60, P<0.001) compared to T790M mutation-negative patients. In the plasma ctDNA subgroup, acquired T790M mutation decreased the OS (HR 1.87, P<0.001).
Conclusion: Pretreatment T790M mutation was associated with worse PFS and OS in patients with advanced NSCLC treated with EGFR-TKIs, while acquired T790M mutation was associated with longer PFS and PPS than T790M mutation-negative NSCLC. The effects on OS were different between acquired T790M mutation detected from rebiopsy of tumor tissue and that detected from plasma ctDNA.

Keywords: epidermal growth factor receptor, T790M, non-small cell lung cancer, pretreatment, mutation

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