Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis

Abstract

Non-small-cell lung cancer (NSCLC) with mutations in the epidermal growth factor receptor (EGFR) is a distinct subgroup of NSCLCs that is particularly responsive to EGFR tyrosine-kinase inhibitors (TKIs). A weighted pooled analysis of available studies was performed to evaluate clinical outcome in patients with EGFR-mutated NSCLC who were treated with chemotherapy or EGFR TKIs. Median progression-free survival (PFS) times were pooled from prospective or retrospective studies that evaluated chemotherapy or single-agent EGFR TKIs (erlotinib or gefitinib) in patients with NSCLC and EGFR mutations. Among the studies identified for inclusion in the analysis, 12 evaluated erlotinib (365 patients), 39 evaluated gefitinib (1069 patients) and 9 evaluated chemotherapy (375 patients). Across all studies, the most common EGFR mutations were deletions in exon 19 and the L858R substitution in exon 21. In the weighted pooled analysis, the overall median PFS was 13.2 months with erlotinib, 9.8 months with gefitinib and 5.9 months with chemotherapy. Using a two-sided permutation, erlotinib and gefitinib produced a longer median PFS versus chemotherapy, both individually (P= 0.000 and P= 0.002, respectively) and as a combined group (EGFR TKI versus chemotherapy, P= 0.000). EGFR TKIs appear to be the most effective treatment for patients with advanced EGFR-mutant NSCLC. Ongoing prospective trials comparing the efficacy of first-line chemotherapy and EGFR TKIs in EGFR-mutant disease should provide further insight into the most appropriate way to treat this specific group of patients.

Fig 1

Sites of common activating mutations in exons 18−21 of the epidermal growth factor receptor gene [22, 23].

Fig 2

Flow diagram showing citations retrieved from literature searches and number of trials included in analysis.

Fig 3

Forest plot showing analysis of median pooled PFS or TTP and 90% accuracy intervals during treatment with single-agent erlotinib, single-agent gefitinib or chemotherapy, in patients with EGFR-mutant NSCLC.

Fig 4

Forest plot showing pooled analysis of median PFS or TTP and 95% accuracy intervals during treatment with single-agent erlotinib, single-agent gefitinib or chemotherapy, in patients with EGFR-mutant NSCLC.

Fig 5

Funnel plots using PFS or TTP as an outcome for (A) erlotinib; (B) gefitinib and (C) chemotherapy.