Author of

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  P3.01 - Advanced NSCLC (ID 621)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 2
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23865

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    P3.01-006 - Osimertinib in Pretreated EGFR T790M-Positive Non-Small Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis (ID 7905)

    09:30 - 09:30  |  Author(s): J. Lee
    • Abstract
    • Slides

    Background:
    Leptomeningeal carcinomatosis (LC) is a detrimental complication of non-small cell lung cancer (NSCLC). Osimertinib is the current standard therapy for pretreated EGFR T790M-positive NSCLC patients. However, the efficacy of osimertinib for these patients with LC is unknown.
    
    Method:
    Retrospective case series of 5 patients with pretreated EGFR T790M-positive NSCLC who developed LC and received osimertinib therapy in an Expanded Access Program was reviewed. We evaluated the clinical outcomes of these patients.
    
    Result:
    Four female patients and one male patient (age, range 51-67) with EGFR T790M-positive NSCLC and LC received osimertinib therapy at a starting dose of 80 mg/day. EGFR T790M mutation was detected in three re-biopsied specimens and two plasma samples. Four patients had Eastern Cooperative Oncology Group performance status (PS) ≧ 2. One patient received whole-brain radiotherapy after commencing osimertinib therapy. Osimertinib dose escalation to 160 mg/day or 160 mg every other day was administered to 3 patients who did not respond to standard dose therapy. Radiologically decreased leptomeningeal enhancement was seen in 3 out of 4 evaluable patients, and improvement of clinical symptoms was recorded in 2 patients. Two patients died of aspiration pneumonia, and one died of hypoxic respiratory failure of unknown cause. Osimertinib therapy is ongoing in two patients at 80 mg/day for 9 and 10 months, respectively, with good tolerability.
    
    Conclusion:
    Osimertinib is well tolerated even in patients with poor PS. Clinical benefits were seen in some patients, and the optimal dose should be explored.
    
    

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    P3.01-074 - Genomic Analysis of Tumor and Plasma in T790M Mutant Positive EGFR Lung Cancer Patients before and after Osimertinib Treatment (ID 9224)

    09:30 - 09:30  |  Author(s): J. Lee
    • Abstract

    Background:
    Osimertinib is a third-generation, central nervous system active epidermal growth factor receptor (EGFR) – tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-sensitising and EGFR T790M resistance mutations. Osimertinib is approved for EGFR mutation positive non small cell lung cancer (NSCLC) patients who develop EGFR T790M resistant mutation and resistant to prior EGFR TKI. Osimertinib resistance pattern and clinical outcome after osimertinib treatment are undergoing intensive investigation.
    
    Method:
    Seventy-one EGFR-TKI resistant patients received osimertinib in the AURA study in one medical center. We excluded patients treated as first-line or who do not have detectable T790M mutation. We collect available data of pre-osimertinib treatment plasma and tissue and post-osimertinib plasma, tissue samples and tested for EGFR, HER2, K-ras, B-raf, mutations, ALK fusion and cMET or HER2 gene amplification. Clinical and pathological characteristics before and after osimertinib treatment were collected.
    
    Result:
    Of the 53 T790M-positive patients, 6 did not progress. Three and 18 patients discontinued osimertinib due to side effect or progression, respectively; 26 received osimertinib beyond progression (1.1 to 20.5 months); 7 patients received osimertinib combination after progression. Fourteen patients are still alive. Median progression-free survival(PFS), overall survival(OS) and post-progression survival (PPS) were 11.1 months, 16.9 months and 5.0 months, respectively (only progression patients). In 47 progressive patients, post progression EGFR plasma tests were available in 40 patients. T790M was detected by BEAMing in 12 patients (4 patients combined with C797S) and not detected in 28 patients (70%). OS and PPS was longest for patients with no detectable EGFR activating mutation and T790M in the plasma before and/or after osimertinib treatment. Patients who lost detectable T790M but maintained activating EGFR mutation in the plasma had shortest osimertinib PFS. Post progression tissue sample or pleural effusion tumor cells were available in 22 patients. Two patients developed small cell transformation, one patient developed squamous cell carcinoma. Post progression tissue or effusion genomic tests were performed (N= tested patient number) and showed T790M+ in 9 patients(N=18), C797S in 2 (N=12), cMET amplification in 5 (N=10), B-Raf V600 mutation in 1 (N=13), K-ras mutation in 1 (N=13) and no ALK, ROS1 and RET fusions.
    
    Conclusion:
    Heterogeneous resistance mechanisms develop after osimertinib treatment, in tumors retain T790M or losing T790M. Patients who have no detectable activating EGFR mutations in the plasma had best survival outcomes. Loss of T790M but maintainance activating EGFR mutations in the plasma correlated with short osimertinib PFS.