RETRACTED ARTICLE: The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Molecularly Selected Patients with Non-Small Cell Lung Cancer: A Meta-Analysis of 30 Randomized Controlled Trials
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To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in molecularly selected patients with advanced non-small cell lung cancer (NSCLC), we performed this pooled analysis.
Randomized trials of EGFR-TKIs as treatment for advanced NSCLC were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs in the selected patients by EGFR-mutation status were calculated.
Out of 2134 retrieved articles, 30 randomized controlled trials (RCTs) enrolling more than 4053 patients with wild-type EGFR tumors and 1592 patients with mutant EGFR tumors were identified. For EGFR mutant patients, EGFR-TKIs treatment improved progression-free survival (PFS) compared with chemotherapy: the summary HRs were 0.41 (p < 0.00001) for the first-line setting and 0.46 (p = 0.02) for second/third-line setting, respectively. Also, the same superior trend was found with TKIs maintenance over placebo (HR = 0.14, p < 0.00001) and with TKIs combined with chemotherapy over chemotherapy (HR = 0.49, p = .002) in both the first-line and maintenance therapy settings. For EGFR wild-type patients, EGFR-TKIs have fared worse than chemotherapy in the first-line setting (HR = 1.65, p = .03) and in the second/third-line setting (HR = 1.27, p = .005). However, EGFR-TKIs maintenance still produced a reduction of 19 % in the risk of progression over placebo (HR = 0.81, p = .02). Furthermore, EGFR-TKIs added to chemotherapy as first-line treatment resulted in an improvement of PFS over chemotherapy alone in such wild-type EGFR patients (HR = 0.82, p = .03). In overall survival (OS) analysis, only EGFR-TKIs single agent was inferior to chemotherapy in EGFR wild-type patients (HR = 1.13, p = .02). No statistically significant difference in terms of OS was observed in any other subgroup analysis.
For EGFR mutant patients, EGFR-TKIs therapy produced a prominent PFS benefit in all settings. Among EGFR wild-type patients, EGFR-TKIs were inferior to chemotherapy both for first-line treatment and for second/third-line treatment. However, EGFR-TKIs maintenance and addition of EGFR-TKIs to chemotherapy could provide additive benefit over chemotherapy alone in such EGFR wild-type patients.
KeywordsOverall Survival Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Mutation Status Factor Receptor Tyrosine Kinase Inhibitor Platinum Doublet Chemotherapy
We are indebted to Yanhua Sun for assistance with data analysis and critiquing the manuscript.
Conflict of Interest Statement
Jin Liu, Zhixin Sheng, Yanxia Zhang and Guixin Li declare no competing financial interests, and did not receive any financial support.
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