Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors As First-line Treatment in Advanced Nonsmall-cell Lung Cancer

Purpose Of Review: Classic activating mutations in the form of deletions in exon 19 or a missense mutation L858R in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) predict dramatic responses to EGFR tyrosine kinase inhibitors such as gefitinib and erlotinib. We review here the clinical benefits of targeted therapy with erlotinib and gefitinib in white and Asian nonsmall-cell lung cancer patients.

Recent Findings: Two separate analyses of pooled data from small phase II prospective studies show that therapy with gefitinib and erlotinib induces responses in over 70% of nonsmall-cell lung cancer patients harboring classic EGFR mutations, with progression-free survival ranging from 9 to 13 months and median survival of around 23 months. Two separate studies in white and Asian patients have recently confirmed that these subgroups of patients attain response rates of 70% with erlotinib and gefitinib, including complete responses, progression-free survival of up to 14 months, and median survival of up to 27 months. The serial monitoring of EGFR mutations in the blood will permit the assessment of molecular responses and be an important tool for the surveillance of clinical progression.

Summary: Nonsmall-cell lung cancer with EGFR mutations constitute a new entity with a unique opportunity for further refinement of different genetic subgroups among patients with EGFR mutations, requiring different personalized treatment strategies. Despite the impressive outcomes attained with EGFR tyrosine kinase inhibitors, patients with EGFR mutations at present require continuous treatment, and only a fraction of these patients will reach sustainable long-term survival.