• Ning Zhao, Xu-Chao Zhang, Hong-Hong Yan, Jin-Ji Yang, and Yi-Long Wu.
• Guangdong Cardiovascular Institute, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, PR China; Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, PR China.
• Lung Cancer. 2014 Jul 1; 85 (1): 66-73.

BackgroundEGFR mutation status is closely related to the efficacy of EGFR-TKIs in advanced non-small cell lung cancer (NSCLC). EGFR-TKIs have become the standard first-line treatment for advanced EGFR-mutation NSCLC, while for EGFR wild-type tumors, the preferred first-line treatment is chemotherapy. However, the efficacy of EGFR-TKIs as second-line treatment in EGFR wild-type NSCLC remains controversial. We sought to evaluate the effectiveness of EGFR-TKI as second-line treatment in EGFR wild-type NSCLC.MethodsRandomized controlled trials that compared EGFR-TKIs with chemotherapy in previously treated advanced NSCLC with wild-type EGFR were included. We performed a meta-analysis to evaluate the effectiveness of EGFR-TKIs compared with standard chemotherapy. The endpoints were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).ResultsSix randomized controlled trials with a total of 990 patients with wild-type EGFR were included: 499 in the EGFR-TKIs group and 491 in the chemotherapy group. The results indicated that in the second-line treatment of EGFR wild-type advanced NSCLC, PFS was significantly inferior in the EGFR-TKIs group versus the chemotherapy group (HR=1.37, 95% CI=1.20-1.56, P<0.00001). However, this significant difference did not translate into OS (HR=1.02, 95% CI=0.87-1.20, P=0.81). ORR tended to favor chemotherapy but there was no significant difference compared with EGFR-TKI (RR=1.77, 95% CI=0.90-3.50, P=0.10).ConclusionsChemotherapy improves PFS significantly but not OS, compared with EGFR-TKIs as a second-line treatment in advanced NSCLC with wild-type EGFR. Whether EGFR-TKIs should be used in EGFR wild-type patients should be considered carefully.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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