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Epidermal growth factor receptor (EGFR)-mutant non-small cell lung
cancer (NSCLC) is a clinically important driver alteration
affecting approximately one-third of lung cancer patients.
Treatments for EGFR-exon 19 deletion and exon 21 L858R NSCLC have
evolved over the last decade from first-generation reversible
tyrosine kinase inhibitors (TKI) to third-generation irreversible
TKIs, of which osimertinib has been the widely accepted as
first-line therapy. Despite survival improvement seen with
osimertinib and its efficacy against acquired T790M mutation,
resistance through on-target and off-target pathways eventually
develop. This Element describes the structural biology and
pathophysiology of EGFR-mutant NSCLC and discusses past, current,
and future treatment options in the metastatic, neoadjuvant, and
adjuvant settings. It describes the biology and recently approved
treatment for EGFR-exon 20 insertion mutation and the treatment for
the uncommon exon 18 (G719X), 20 (S768I), and 21 (L861Q) mutations.
It also outlines the promising clinical applications of circulating
tumor DNA (ctDNA).
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