Targeting Classical EGFR Mutations in Lung Cancer: Twenty Years of Progress and Beyond

Abstract

Simple Summary Classical EGFR mutations have transformed the management of non-small cell lung cancer across metastatic, resectable, and unresectable locally advanced settings. This review traces the evolution from early-generation EGFR tyrosine kinase inhibitors to osimertinib and contemporary combination regimens, and summarizes central nervous system management, radiotherapy, acquired resistance, and biomarker-guided treatment. It also addresses unresolved sequencing after FLAURA2 or MARIPOSA, histologic transformation, fourth-generation EGFR inhibitors, nucleic-acid delivery platforms, and data-enabled precision oncology.