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A. Yamada



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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-005 - Early versus Late Brain Metastases in Wild Type and Mutation Positive EGFR Patients (ID 416)

      09:30 - 09:30  |  Author(s): A. Yamada

      • Abstract
      • Slides

      Background:
      Brain metastasis (BM) in NSCLC is a negative prognostic indicator. Historically, the median survival from diagnosis of BM has been reported as 6 m. The prognostic significance of BM however, may be altered in the setting of EGFR mutated disease. The timing of BM development may also influence survival outcomes. We evaluated the difference between early (<= 6 months from diagnosis) versus late (> 6 months) BM, in EGFR wild type (WT) and mutant (MT) with respect to radiographic patterns and the impact on survival.

      Methods:
      The British Columbia Cancer Agency provides cancer care to a population of 4.6 million. A retrospective study was conducted of referred patients with stage IV non squamous NSCLC who underwent whole brain radiotherapy and/or surgical resection of brain metastasis with known EGFR mutation status from Mar 2010 - Dec 2012. The data was analyzed by WT and MT, early and late BM groups to characterize the radiographic patterns and overall survival (OS) from initial NSCLC diagnosis (dx) and BM dx.

      Results:
      430 patients were identified: 327 WT patients (206 early vs 121 late) and 103 MT (65 early vs 38 late). Pattern of BM in WT early vs late showed no difference in size of largest BM, number of metastases, cerebral edema. Leptomeningeal disease was more frequent in WT late disease (2% vs 8% p=0.01). Pattern of BM in MT early vs late showed no difference in size of largest BM, cerebral edema or leptomeningeal disease. There was a trend to miliary pattern disease in MT late BM (p=0.058). Median OS from initial dx in EGFR WT was early: 7.1 m vs late: 24.9 m (p<0.001) and OS from BM dx early: 6.3 m vs late: 4.9 m (p=0.67). Median OS from initial dx in EGFR MT was early: 19.9 m vs late: 25.6 m (p=0.39) and OS from BM dx early: 19.2 m vs late: 3.9 m (p<0.001). Cox proportional hazards (CPH) model showed in the EGFR WT receipt of chemotherapy and late BM were associated with better survival. CPH in EGFR MT demonstrated that good PS and systemic treatment but not BM timing were predictive of better outcomes.

      Conclusion:
      Brain metastases in EGFR WT disease is a significant negative prognostic indicator with early dx associated with poor survival. In contrast, in EGFR mutation positive disease, the overall survival from diagnosis is the same regardless of the development of early or late brain metastases. This outcome may reflect the importance of systemic control and the penetrance of EGFR TKIs across the blood brain barrier.

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