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NSCLC — SCE Medical Oncology MCQ

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HardLung CancerNSCLCSCE Medical Oncology

A 62-year-old man with EGFR-mutant NSCLC progressed on first-line osimertinib. Tissue re-biopsy shows MET amplification as the resistance mechanism. What combination therapy is being evaluated in this setting?

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Correct answer: B — Osimertinib + savolitinib (MET inhibitor)

MET amplification is a common osimertinib resistance mechanism (~15-20%). The SAVANNAH and TATTON trials showed that combining osimertinib with savolitinib (selective MET inhibitor) achieves responses in MET-amplified osimertinib-resistant NSCLC. Tepotinib + osimertinib (INSIGHT 2) is another MET-directed combination. This bypass-track resistance mechanism allows continued EGFR inhibition while simultaneously targeting the MET pathway.

Reference: ESMO 2024 NSCLC Guidelines; SAVANNAH Sequist et al Lancet Oncol 2023