The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor: A Meta-analysis of 25 RCTs.

OBJECTIVE: To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) patients with wild-type (WT) EGFR tumors, we performed an indirect meta-analysis to assess the treatment effects of EGFR-TKIs in such patients.

METHODS: We searched for randomized controlled trials in Medline, Embase, the Cochrane controlled trials register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Effect measures used were hazard ratios (HR) for progression-free survival (PFS) and overall survival.

RESULTS: Out of 2134 retrieved articles, 25 randomized controlled trials including more than 4467 patients were identified. This pooled analysis showed the inferior efficacy of TKI over chemotherapy among patients with WT EGFR NSCLC in terms of PFS (HR, 1.37; 95% confidence interval [CI]: 1.10, 1.72; P=0.006). When used as first-line treatment, TKIs have also fared worse than chemotherapy when compared with standard platinum doublet regimens in patients with WT EGFR in terms of PFS (HR, 2.15; 95% CI: 1.68, 2.76; P<0.001). And, the same inferior trend was found with TKIs in those trials of second-line/third-line treatment in terms of PFS (HR, 1.35; 95% CI: 1.13, 1.61; P<0.001). However, according to the pooled results, EGFR-TKIs still produced a reduction of 19% in the risk of progression over placebo in such WT EGFR patients ineligible for further chemotherapy (HR, 0.81; 95% CI: 0.68, 0.97; P=0.02). Furthermore, addition of EGFR-TKI to chemotherapy resulted in an improvement of PFS over chemotherapy alone (HR, 0.83; 95% CI: 0.71, 0.96; P=0.01).

CONCLUSIONS: Among patients with advanced NSCLC harboring WT EGFR, EGFR-TKIs were inferior to standard chemotherapy both for first-line treatment and for second-line/third-line treatment, but still superior to placebo in patients unfit for further chemotherapy. And, addition of EGFR-TKIs to chemotherapy could provide additive benefit over chemotherapy alone in such patients.