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Akihiro Tamiya

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-60 - Afatinib in EGFR Mutation-Positive NSCLC: Activity in Patients with Brain Metastases, and Impact on CNS Progression/Spread (ID 1664)

      10:15 - 18:15  |  Author(s): Akihiro Tamiya

      • Abstract
      • Slides


      In the LUX-Lung 3 and 6 trials, first-line afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with EGFR mutation-positive (EGFRm+) NSCLC and baseline brain metastases (hazard ratio [HR], 0.50; P=0.0297).1 In LUX-Lung 7, similar PFS improvement with afatinib versus gefitinib was observed in patients with, and without, brain metastases (HR, 0.76 and 0.74; Pint=0.93).2 The aims of this study were to assess: i) the impact of afatinib on central nervous system (CNS) progression or metastatic spread in LUX-Lung 3, 6, and 7; ii) efficacy of afatinib in patients with brain metastases in a similar setting to ‘real-world’ practice.


      Competing risk analysis of CNS/non-CNS progression or death was performed in patients who received afatinib in LUX-Lung 3, 6, and 7, based on the cumulative frequency of the event of interest versus the competing risk event. Separate analysis was performed of an Asian phase IIIb study, which assessed afatinib in a broad population of EGFR TKI-naïve patients with EGFRm+ NSCLC (NCT01953913).3 PFS and time-to-symptomatic progression (TTSP) in patients with baseline brain metastases were calculated by Kaplan–Meier methodology.


      In patients with baseline brain metastases receiving afatinib in LUX-Lung 3 and 6 (n=48; median follow-up: 10.3 months), the risk of CNS progression was 40% lower than the risk of extracranial progression; 31.3%/52.1% of patients had CNS/non-CNS progression, respectively. In patients without baseline brain metastases receiving afatinib in LUX-Lung 3, 6, and 7 (n=485; median follow-up: 13.0 months), the risk of de novo CNS/non-CNS progression was 6.4%/78.4%. Cumulative risk of CNS/non-CNS progression was 1.3%/17.2% at 6 months and 2.6%/41.2% at 12 months. In the Asian phase IIIb study, there was no difference in PFS (median 10.9 vs 12.4 months; P=0.18) or TTSP (median 14.8 vs 15.4 months; P=1.0) between patients with (n=92) or without (n=387) brain metastases.


      Competing risk analyses of LUX-Lung 3, 6, and 7 suggest that afatinib delays the onset/progression of brain metastases. Real-world data are consistent with LUX-Lung 3, 6, and 7, and support the use of afatinib in patients with EGFRm+ NSCLC and baseline brain metastases.

      1. Schuler, M. et al. J Thorac Oncol 2016;11:380‒90

      2. Park, K. et al. Lancet Oncol 2016;17:577‒89

      3. Wu YL, et al. J Thorac Oncol 2017;12(suppl 2):abstract P3.01-036

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