Current treatment landscape for patients with non-small cell lung cancer with common EGFR mutations

Common EGFR mutations including exon-19 deletions and the L858R point mutation in exon 21 constitute predominant actionable genomic alterations in individuals with non-small cell lung cancer (NSCLC). The introduction of EGFR tyrosine kinase inhibitors (TKIs) has fundamentally changed the treatment landscape for such patients by improving both progression-free survival (PFS) and overall survival (OS). Among EGFR-TKIs, third-generation agents such as osimertinib have shown marked efficacy and favorable safety profiles and have become the standard of care in the first-line setting. The combination of osimertinib with platinum-based chemotherapy has recently been shown to improve PFS compared with osimertinib monotherapy in the FLAURA2 trial. Similarly, the MARIPOSA trial demonstrated clinical benefit of the combination of the EGFR-MET bispecific antibody, amivantamab, with the third-generation EGFR-TKI, lazertinib, further supporting the use of combination therapies as first-line treatment for EGFR-mutated NSCLC. Despite these advances, however, challenges such as brain metastases remain substantial barriers to successful treatment outcomes. Management of patients with such metastases often requires a multidisciplinary approach that integrates systemic treatment with local interventions such as radiation therapy. Finally, circulating tumor DNA has emerged as a promising biomarker for real-time monitoring of treatment response and evolution of drug resistance mechanisms. Analysis of such biomarkers can facilitate dynamic and personalized therapeutic adjustments, potentially improving outcomes. This review provides a comprehensive overview of the latest clinical evidence supporting therapeutic advances in the management of EGFR-mutated NSCLC, emphasizing the importance of tailoring treatment strategies based on tumor biology, patient-specific factors, and evolving therapeutic options.