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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Comparing overall survival between first generation EGFR-TKIs and chemotherapy in lung cancer patients with
Wei Deng1, Yuanyuan Lei1, Siyang Liu2
1Second Clinical Medial Committee, Southern Medical University, Guangzhou 510515, China; Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Objective:
Combined overall survival (OS) analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor (EGFR) exon 19 deletions (Del19) would benefit from first-line second generation EGFR tyrosine kinase inhibitors (TKIs) afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups.
Methods:
Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios (HRs). All measures were pooled using randomeffects models and 95% confidential interval (95% CI) was calculated.
Results:
A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials (RCTs), first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy (pooled HRTKI/Chemo for Del19: 0.82, 95% CI: 0.64-1.06, P = 0.14; pooled HRTKI/Chemo for L858R: 1.15, 95% CI: 0.85-1.56, P = 0.38). Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference (pooled HR19/21: 0.88, 95% CI: 0.67-1.16, P = 0.37).
Conclusions:
Among patients with advanced non-small cell lung cancer (NSCLC) harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.
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