Monitoring Response and Resistance During Osimertinib-Based Therapy in EGFR-Mutant NSCLC

This segment examines best practices for monitoring treatment response and evaluating disease progression during osimertinib-based therapy for EGFR-mutant non-small cell lung cancer (NSCLC). Drs. Mark Socinski and Susan Scott discuss surveillance strategies, including early CT imaging, routine longitudinal imaging, and brain MRI to monitor for central nervous system (CNS) progression and identify oligoprogression that may be amenable to local therapy while maintaining effective systemic treatment. The conversation then shifts to molecular retesting at disease progression, emphasizing the complementary roles of plasma and tissue biopsy to identify histologic transformation and acquired resistance mechanisms. Although actionable alterations such as MET amplification, RET fusions, and other genomic changes are identified in a minority of patients, the experts stress that comprehensive molecular profiling remains essential for guiding treatment selection, identifying clinical trial opportunities, and distinguishing transformation to small cell, squamous, or other histologies that require a fundamentally different therapeutic approach.