EGFR-Mutated NSCLC: Optimizing Treatment from First-Line Selection to Second-Line Sequencing

Treatment of EGFR-mutated advanced non-small cell lung cancer has moved well past a single tyrosine kinase inhibitor, and the decisions have grown correspondingly harder. This series works through them in sequence. It opens with risk stratification, including how often TP53 co-mutations appear and what they should change, then examines the clinical and molecular factors that determine whether a patient starts on monotherapy or a combination, weighing tumor burden and metastatic sites against age, comorbidities, and what a patient is willing to accept. Second-line discussion covers platinum rechallenge, the choice between datopotamab deruxtecan and amivantamab plus chemotherapy in the absence of a head-to-head trial, and what emerging antibody-drug conjugate combinations would need to demonstrate to change practice. Later segments turn to the toxicities that actually interrupt treatment, the multidisciplinary support required to manage them, and the testing, trial access, and reimbursement barriers that shape care outside academic centers.