Cancer Res Treat.  2023 Jan;55(1):344-349. 10.4143/crt.2021.1603.

Osimertinib Combined with Systemic Chemotherapy for EGFR Mutant, T790M-Negative, Non–Small Cell Lung Cancer Patients Who Develop Leptomeningeal Metastases with Extracranial Progression to Prior EGFR TKI

  • 1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea


Leptomeningeal metastasis (LM) is a rare but fatal clinical condition with a short survival time. The incidence of LM from epidermal growth factor receptor mutant (EGFRm) non–small cell lung cancer (NSCLC) has increased due to the limited efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the central nervous system (CNS). Osimertinib is a third-generation, irreversible, CNS penetrant, oral EGFR TKI that demonstrates promising efficacy in CNS metastases regardless of T790M. Herein, we report four cases of T790M-negative EGFRm NSCLC patients treated with osimertinib combined with systemic chemotherapy, who progressed on prior EGFR TKI and developed LM with extracranial lesions. The combination treatment was well tolerated, and the mean overall survival from LM diagnosis was 14.7 months (95% confidence interval, 10.4 to 19.0). These results suggest that osimertinib combined with systemic chemotherapy would be a reasonable treatment option for T790M-negative EGFRm NSCLC patients who develop LM with extracranial progression to prior EGFR TKI. A further prospective study is warranted.


Leptomeningeal metastasis; EGFR mutant NSCLC; Osimertinib; Systemic chemotherapy


  • Fig. 1 The brain magnetic resonance imaging (MRI) and chest computed tomography (CT) imaging before and after osimertinib administration. The gray-colored arrows indicate before (left) and after (right) osimertinib administration, and the red-colored arrows point out the leptomeningeal metastasis. Brain MRI and chest CT imaging in case 1 (A), case 2 (B), case 3 (C), and case 4 (D).



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