EGFR-Mutated Non-Small Cell Lung Cancer — Proceedings from a Session Held in Conjunction with the 2026 ASCO Annual Meeting

The management of metastatic EGFR-mutated non-small cell lung cancer has shifted from osimertinib monotherapy to combination regimens, specifically chemotherapy plus osimertinib or amivantamab plus lazertinib. These combinations demonstrate superior progression-free and overall survival, particularly in high-risk subgroups such as those with brain metastases. Clinical decision-making now prioritizes managing toxicities—including skin rashes, paronychia, and stomatitis—through prophylactic strategies like the COCOON regimen and subcutaneous amivantamab administration. Resistance mechanisms remain complex and heterogeneous, necessitating repeat tissue or liquid biopsies to identify targetable alterations like MET amplification or secondary EGFR mutations. Emerging therapies, including TROP2-targeted antibody-drug conjugates like datopotamab deruxtecan and bispecific antibodies such as ivanesimab, offer promising avenues for patients progressing on standard targeted treatments. Maintaining EGFR-TKI inhibition while integrating these novel agents remains a critical strategy for extending disease control in this evolving clinical landscape.