Epidermal growth factor receptor–mutated non–small cell lung cancer: a clinical approach

The discovery of EGFR mutations has revolutionized the treatment of metastatic non−small cell lung cancer (NSCLC), allowing for tyrosine kinase inhibitors (TKIs) to be developed and used in this setting. TKIs have shown consistent improvement in progression-free survival over platinum-based chemotherapy, which otherwise serves as the standard backbone of treatment for NSCLC. Recently, a third-generation EGFR TKI, osimertinib, showed an improvement in progression-free survival and overall survival (OS), when compared with two first-generation TKIs, and is the current first-line standard of care treatment in the United States. This chapter highlights the clinical data for EGFR mutations, analyzing the key clinical trials and discussing novel treatment approaches (including combinations with chemotherapeutic antiangiogenesis and targeted agents). The chapter also focuses on the importance of molecular testing in advanced NSCLC, comparing tissue and plasma-based testing and reviewing the available data on resistance mechanisms, both in the first- and subsequent-line settings. Lastly, we review the current challenges in treatment of EGFR-mutated NSCLC, including post osimertinib therapy and the issues with using immunotherapy.