Author of

• 15751

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  MINI 26 - Circulating Tumor Markers (ID 148)

  • Event: WCLC 2015
  • Type: Mini Oral
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:M. Macmanus, C. Aggarwal
  • Coordinates: 9/09/2015, 16:45 - 18:15, 205+207

  • 15763

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    MINI26.13 - Serial ctDNA Assessment of Response and Resistance to EGFR-TKI for Patients with EGFR-L858R Mutant Lung Cancer from a Prospective Trial (ID 3107)

    17:50 - 17:55  |  Author(s): H.-. Tu
    • Abstract
    • Presentation
    • Slides

    Background:
    Plasma circulating tumor DNA (ctDNA) has been widely accepted as a form of liquid biopsy to detect EGFR mutations in NSCLC for its high concordance rate with tumor tissues. There are some retrospective studies about the ctDNA quantitative changes of EGFR mutations in EGFR-TKI treatment, but there is no report about serial ctDNA assessment of response and resistance to EGFR-TKI by detecting the dynamic changes of EGFR mutations during the whole course of EGFR-TKI treatment based on prospective clinical trial.
    
    Methods:
    Based on a randomized trial initiated to compare erlotinib with gefitinib in advanced NSCLC harboring EGFR exon 21 L858R mutation in tumor tissues (CTONG0901, NCT01024413), we prospectively collected serial plasma samples as preplanned schedule (baseline, one week after treatment, one month after treatment and then every 8 weeks until disease progression) and quantitatively detected EGFR L858R mutation in ctDNA by using fluorescence quantitative polymerase chain reaction. We made a serial ctDNA assessment of response and resistance to EGFR-TKI and its correlation with survival outcomes. Four patients’ serial plasma samples were selected to undergo next generation sequencing (NGS).
    
    Results:
    From 108 patients enrolled in the trial, serial plasma of 80 patients were collected as schedule and tested the quantity of L858R. As a whole, the quantity of L858R decreased to the lowest level when patients achieved best response to EGFR-TKI and increased to the highest level when disease progressed. Further analysis by Ward's Hierarchical Clustering Method showed that the dynamic changes of quantity of L858R could be categorized into two groups, Ascend Group and Stable Group (Figure 1A). Median progression-free survival (PFS) was 11.1 months (95%CI=6.6-15.6) and 7.5 months (95%CI=1.4-13.6) in two groups, respectively (HR=0.57, 95%CI=0.34-0.97, P=0.035) (Figure 1B). Median overall survival was 20.1 months (95%CI=15.7~24.5) vs. 16.4 months (95%CI=13.3~19.6) (HR=0.73, 95% CI =0.38~1.38, P=0.322). In multivariate Cox proportional hazards regression analysis, changing group was independent predictive factor for PFS. In plasma samples of 4 patients underwent NGS, similar dynamic changing characteristics were confirmed and more genetic mutations were found. Detailed data will be presented on site.Figure 1
    
    
    
    Conclusion:
    This is the first report about serial ctDNA assessment of response and resistance to EGFR-TKI by detecting the dynamic changes of EGFR mutation based on a prospective clinical trial. The quantity of plasma L858R has different changing patterns during EGFR-TKI treatment and higher L858R mutation abundance on EGFR-TKI resistance is correlated with longer PFS.
    
    

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