Management of eGFR-Mutant non-small cell Lung cancer: Focus on Gefitinib

Abstract

Gefitinib is a first generation, reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and EGFR TKIs, such as gefitinib and erlotinib, have yielded dramatic and durable responses in approximately 75% of of non-small cell lung cancer (NSCLC) patients whose tumor has an activating EGFR mutation. EGFR mutations are found in approximately 10%–15% of lung cancers in Caucasians, and they are more frequent in female patients, patients with adenocarcinoma, patients who are never- smokers or have a history of light-smoking, and patients with Asian ethnicity. Recent phase III trials comparing gefitinib with standard chemotherapy have demonstrated a similar survival benefit of gefitinib in patients with NSCLC and improved quality of life both in a first-line setting (IPASS; comparing gefitinib with carboplatin/paclitaxel) and a previously-treated setting (INTEREST; comparing gefitinib with docetaxel). Subset analyses of the data obtained in these studies showed that in patients with EGFR-mutant NSCLC gefitinib yielded a higher response rate, longer progression-free survival, and similar overall survival than standard cytotoxic chemotherapy did. The toxicity of EGFR TKIs is generally milder than that of standard cytotoxic chemotherapy. This review focuses on gefitinib, and issues in the management of EGFR-mutant NSCLC are discussed.