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Osimertinib LM — SCE Medical Oncology MCQ

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ModerateLung CancerOsimertinib LMSCE Medical Oncology

A 60-year-old man with EGFR-mutant NSCLC on osimertinib develops leptomeningeal metastases (LM) confirmed by CSF cytology. His extracranial disease is controlled. What makes osimertinib specifically advantageous for LM?

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Correct answer: D — Osimertinib has excellent CNS penetration (CSF:plasma ratio ~1-2%) and demonstrated activity in EGFR-mutant leptomeningeal disease in the BLOOM study

Osimertinib has the best CSF penetration of all EGFR TKIs (CSF concentration ~1-2% of plasma — sufficient for EGFR-mutant cancer cells). The BLOOM study showed osimertinib 160 mg (double dose) achieved ORR ~60% in EGFR-mutant leptomeningeal disease. Even at standard 80 mg dose, osimertinib has meaningful CSF concentrations. This represents a major advance for EGFR-mutant NSCLC with LM, which historically had very poor prognosis (median survival 3-6 months). Intrathecal chemotherapy may be complementary.

Reference: ESMO 2024 NSCLC; BLOOM Yang et al JCO 2020