Progressing on Frontline Therapy: Resistance Mechanisms and Second-Line Options

In this segment, the panel addresses what happens when a patient progresses on frontline EGFR-directed therapy, starting with how to approach repeat molecular profiling and what resistance mechanisms to look for. You will hear why tissue and liquid biopsy play complementary roles at progression, when concordance between the two is high and when it is not, and why the pattern and pace of progression matter as much as the molecular result. The panel then walks through the actionable resistance mechanisms most relevant in practice, including MET alterations and secondary EGFR mutations, and discusses how the availability of multiple second-line options in this space requires an individualized approach based on what the patient received upfront, how long ago they received it, and what their goals and tolerance for side effects are.