The development of tyrosine kinase inhibitors (TKIs) for late-stage epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) represented a drastic change in the treatment of late-stage lung cancer. Drug resistance develops after a certain period of first-line TKI treatment, which has led to decades of changing treatment guidelines for EGFR-mutant NSCLC. This study discussed the potential mechanisms of drug resistance against first-line TKI treatment and potential successive treatment strategies. Next-generation sequencing (NGS) may play a role in the evaluation of drug resistance in first-line TKI treatment. Emerging combination regimens and ongoing trials were discussed. Potential future strategies for treatment and for the management of drug resistance were proposed in this study.
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