S16 Ep23: Show Me the Data™: Post-TKI Sequencing in EGFR-Mutated NSCLC—Optimizing Current Strategies and Preparing for New Treatment Modalities

Sequencing systemic therapy for EGFR-mutated non-small cell lung cancer following progression on first-line tyrosine kinase inhibitors requires a precise, molecularly-driven approach. Repeat biopsies, whether liquid or tissue-based, are essential to identify actionable resistance mechanisms such as MET amplification or histological transformation to small cell lung cancer. For patients with oligoprogression, local therapies like radiation combined with continued TKI therapy remain standard. In cases of systemic progression, clinicians increasingly utilize MET-targeted therapies, platinum-based chemotherapy, or emerging bispecific antibodies like amivantamab and ivonescimab. MET amplification copy numbers, particularly those exceeding six, guide treatment selection, while small cell transformation necessitates a shift to platinum-etoposide regimens. Recent clinical data underscores the potential of PD-1/VEGF bispecifics to improve outcomes in TKI-refractory patients, particularly those with brain metastases, offering a promising alternative to traditional chemotherapy-based strategies.