Second-Line Sequencing After Frontline Progression in EGFR-Mutated NSCLC

August 20, 2026

This segment takes up the question community oncologists ask most often in EGFR-mutated advanced non-small cell lung cancer: what follows osimertinib plus chemotherapy. Individual disease course matters more than a default algorithm. Because many patients on the FLAURA2 regimen stop pemetrexed early for fatigue or other toxicity, platinum doublet rechallenge is reasonable after progression off chemotherapy, while progression soon after platinum exposure prompts more hesitation, and that distinction shapes whether amivantamab is paired with lazertinib or with chemotherapy. The discussion notes that no trial directly compares datopotamab deruxtecan with amivantamab plus chemotherapy, describes their progression-free survival as broadly similar, and points out that neither TROP2 immunohistochemistry nor amplification or overexpression status currently guides selection, leaving prior therapy and clinical trial access as the practical deciders.