Usage of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) in Tumor EGFR Wild-Type or Unknown Non-Small Cell Lung Cancer

Abstract

Targeted therapy for metastatic non-small cell lung cancer (NSCLC) has been actively studied in the last decade. The use of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is considered the standard first-line treatment for metastatic NSCLC patients with tumor EGFR activating mutations, especially after the I-PASS and many similar studies showed longer progression-free survival and better quality of life when these patients received EGFR-TKIs, than when they received platinum-based chemotherapies. Chemotherapy was the remaining option for those patients whose tumor EGFR was wild-type or unknown. Almost all patients who received first-line treatment, either EGFR-TKI or chemotherapy, eventually relapsed and needed second-line salvage therapy. Documented effective second-line therapy for NSCLC patients who had been treated with platinum-based chemotherapy included docetaxel, pemetrexate, and erlotinib. Several phase III randomized trials showed that usage of gefitinib or erlotinib in a second-line or third-line setting was not inferior to docetaxel or pemetrexate treatment. The present review attempts to summarize previous studies of second-line treatment with EGFR-TKI or chemotherapy for NSCLC patients, paying special attention to compare the efficacies between different agents in those patients whose tumor EGFR was wild-type or unknown.