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Toshihiko Yamaguchi

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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-13 - A Phase 2 Trial Assessing Osimertinib Activity Against Leptomeningeal Carcinomatosis in EGFR-Mutant Lung Cancer (Now Available) (ID 470)

      08:00 - 18:00  |  Author(s): Toshihiko Yamaguchi

      • Abstract
      • Slides


      Leptomeningeal carcinomatosis (LMC) occurs in 10 % of EGFR-mutant lung adenocarcinoma (LA). Retrospective studies have suggeted a clinical benefit of osimertinib in treating LMC in patients with EGFR-mutant LA. We conducted a phase 2 prospective trial to demonstrate the clinical efficacy, activity, and LMC-specific mechanisms of resitance to osimertinib in EGFR-mutant LA patients.


      We performed gadalidium-enhanced brain MRIs at the time of enrollment, followed by scheduled brain imaging once every six weeks. Clinical neurological exams were performed every four weeks. Adverse Events (AEs) were assessed by NCI-CTCAE Ver. 4. Cerebral spinal fluid (CSF) and plasma was obtained on day 1 and 21 for all patients. The CSF osimertinib penetration rate was measured by liquid-chromatography mass spectrometry (LC-MSMS) and compared to plasma osimertinib levels. Targeted droplet digital PCR (ddPCR) was used to detect copy number changes of Met and the EGFR C797S mutation in patients CSF-DNA and plasma cell free (cf) DNA.


      We enrolled six pre EGFR-TKI treated EGFR mutant LA with LMC. We observed a LMC-specific progression free survival of 3.7 months and overall survival of 6.2 months or longer with osimertinib. Four and three of six patients showed neurological and radiological responses, respectively. No patients had any AEs greater than grade 3 and all patients continued osimertinib beyond PD. The osimertinib CSF penetration rate was 1.2±0.5%. Met copy number was normal in plasma, but increased in the CSF of 2/6 patients prior to progression. Met copy number was confirmed in 1/6 patients at the time of progression. An aquired EGFR C797S mutation was observed in 1/6 patients prior to progression.



      Osimertinib 80 mg is efficacious in the treatment of LMC in EGFR mutated LA. CSF-specific MET copy number gain and EGFR C797S mutations arise prior to progression in EGFR-mutant LA patients treated with osimeritinib.

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