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EGFR T790M — SCE Medical Oncology MCQ

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EasyLung CancerEGFR T790MSCE Medical Oncology

A 60-year-old woman with metastatic NSCLC has a known EGFR T790M mutation detected on liquid biopsy after progression on first-line gefitinib. What is the clinical significance of T790M?

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Correct answer: A — T790M is the most common acquired resistance mutation to first/second-generation EGFR TKIs; it is specifically targeted by osimertinib

The EGFR T790M 'gatekeeper' mutation accounts for approximately 50-60% of acquired resistance to first/second-generation EGFR TKIs (gefitinib, erlotinib, afatinib). It sterically hinders TKI binding. Osimertinib was originally developed specifically to target T790M (AURA3 trial, NICE TA653). Detection via liquid biopsy (ctDNA) avoids the need for tissue re-biopsy. The adoption of first-line osimertinib (FLAURA) has shifted T790M from a resistance mechanism to a less common clinical scenario.

Reference: NICE TA653 Osimertinib for T790M-positive NSCLC; AURA3; ESMO 2024 NSCLC Guidelines