2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.33 Pulse-dose osimertinib for treatment of leptomeningeal disease or refractory brain metastases in EGFR-mutated non-small cell lung cancer

PP01.33 Pulse-dose osimertinib for treatment of leptomeningeal disease or refractory brain metastases in EGFR-mutated non-small cell lung cancer

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The study explores the efficacy and tolerability of pulse-dose osimertinib in treating leptomeningeal disease (LMD) and refractory brain metastases in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Traditional systemic treatments involve osimertinib doses of 80-160 mg daily, but adverse events (AEs) at these doses often lead to dose reductions or discontinuations. The study specifically aims to evaluate the potential of a pulse-dose regimen (400-560 mg once every 5-7 days) as a viable alternative.<br /><br />This retrospective case series included patients from Stanford University and UC Davis who had metastatic EGFRm NSCLC with either LMD or parenchymal brain metastases. The focus was on those receiving any line of therapy, with or without concurrent systemic or radiation therapies.<br /><br />Results indicated that pulse-dose osimertinib provided a median CNS control duration of 8.2 months. It was particularly beneficial for patients who hadn't previously used osimertinib 160 mg daily. The treatment was well-tolerated, with no grade 3 or higher adverse events reported, and no discontinuations due to toxicity in the monotherapy group.<br /><br />Common dosing strategies were 560 mg once weekly and 400 mg once weekly, with some patients on concurrent therapies such as chemotherapy or bevacizumab. Even in combination therapies, no severe AEs were attributed to osimertinib. The study found that pulse-dose osimertinib might offer an alternative for patients who cannot tolerate higher daily doses due to adverse effects or disease burden.<br /><br />In conclusion, pulse-dose osimertinib presents a promising strategy for managing challenging cases of EGFR-mutated NSCLC with CNS involvement, particularly for those unable to tolerate standard osimertinib dosing.

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Keywords

osimertinib

pulse-dose

leptomeningeal disease

brain metastases

EGFR-mutated NSCLC

tolerability

CNS control

adverse events

retrospective case series

alternative therapy