This review provides a comprehensive update on the evolving landscape of treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, particularly focusing on advances in precision medicine and overcoming acquired resistance. Initial success with first-generation EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC has paved the way for precision oncology and subsequent development of third-generation EGFR TKIs, the current standard of care as first-line therapy in advanced stage NSCLC. Furthermore, a combinational approach of third-generation EGFR TKI with chemotherapy or amivantamab was associated with prolonged progression-free survival. The role of EGFR TKIs also has been investigated in locally advanced and early stage NSCLC, including perioperative and neoadjuvant settings. However, most patients experience acquired resistance, and the resistance mechanism is quite complex and heterogeneous, highlighting the importance of tailored subsequent therapeutic approaches. Overall, this review underscores the dynamic landscape of EGFR-mutated NSCLC treatment, emphasizing the need for personalized strategies to optimize patient outcomes.
Keywords: epidermal growth factor receptor (EGFR); non–small cell lung cancer (NSCLC); resistance; tyrosine kinase inhibitor (TKI).
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