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.

EGFR Tyrosine Kinase Mutation Testing in the Treatment of Non-Small-Cell Lung Cancer

“…An interim analysis showed significantly higher response rates with gefitinib than with carboplatin-paclitaxel (74.5% vs. 29.0%, p < 0.001) and a longer pfs of 10.4 months compared with 5.5 months (hr: 0.357; 95% ci: 0.25 to 0.51; p < 0.001). A recent literature-based meta-analysis confirmed the clinical value of efgr tki therapy in patients with nsclc and EFGR mutations 15 .…”

Biomarker Discovery, Validation and Clinical Application for Patients Diagnosed with Glioma

“…Although patients with the damaged BRAF are non-responsive to the KRAS/BRAF inhibitor, sorafenib, response to the second-generation drug called PLX4720 is favourable (Whittaker et al 2010). Improved outcomes have also been reported in patients with non-small cell lung cancer (NSCLC) harbouring EGFR mutations treated with the tyrosine kinase inhibitors (TKI) erlotinib and gefitinib (Kim et al 2008;Paz-Ares et al 2010).…”

Afatinib treatment in advanced non-small cell lung cancer

“…26 Those patients initially responding to EGFR-TKIs will typically develop resistance leading to relapse of disease (median duration of response 14 months). 27 This is termed secondary or acquired resistance. Mutations in exon 20 of the EGFR kinase domain account for a significant proportion of these cases.…”