EGFR-Mutated NSCLC: Molecular Reassessment at Disease Progression

In this case-based segment, Dr. Sands presents a patient with EGFR-mutated metastatic non-small cell lung cancer who has progressed after first-line combination therapy with an EGFR tyrosine kinase inhibitor and chemotherapy, now with new brain metastases. Dr. Cooper discusses her approach to molecular reassessment at the time of progression, emphasizing the importance of identifying resistance mechanisms to guide subsequent treatment decisions. She highlights the complementary roles of liquid biopsy and tissue biopsy, noting that liquid biopsy offers a less invasive and rapid means of detecting common alterations, while tissue biopsy may be necessary when results are inconclusive or when additional histologic information is needed. The discussion focuses on the identification of actionable resistance pathways, including MET alterations, and how these findings influence treatment sequencing. Overall, this segment underscores the critical role of biomarker-driven decision-making in the management of EGFR-mutated NSCLC after disease progression.