Author of

• 18374

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  P3.02b - Poster Session with Presenters Present (ID 494)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18398

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    P3.02b-024 - Dynamics of EGFR Mutational Load in Urine and Plasma Correlates with Treatment Response in Advanced NSCLC (ID 5529)

    14:30 - 14:30  |  Author(s): T. Tanvetyanon
    • Abstract

    Background:
    NSCLC is a heterogeneous and dynamic disease where testing for key mutations is essential. With the emergence of clonal resistance, obtaining serial biopsies to assist in the real-time treatment decision-making has proven challenging. Molecular assessments of circulating tumor (ct)DNA has been previously shown feasible utilizing blood specimens. Here we additionally investigated the utility of serial urine ctDNA analysis in NSCLC.
    
    Methods:
    This is a prospective observational study of patients with non-squamous, tissue-confirmed EGFR, KRAS or ALK mutant NSCLC preparing to receive a systemic treatment regimen. Urine and blood specimens were collected at baseline, on treatment and at progression for ctDNA analyses. The primary endpoints were correlation between ctDNA and tumor-based molecular results, and measurable change in ctDNA with response by RECIST v1.1. Blood and urine samples were sent to Trovagene for DNA extraction and mutation enrichment NGS.
    
    Results:
    Of the 34 patients enrolled thus far, interim blinded analysis of EGFR activating mutations (L858R, exon 19 deletions) was conducted in 20 patients with EGFR-positive tumors. Of 20 patients, 17 (85%) had detectable concordant EGFR mutation in pre-treatment urine and/or plasma. Of 11 patients with matched serial ctDNA samples, detectable EGFR mutation signal was observed in pre-treatment urine and/or plasma of 9 patients. These 9 patients received first to sixth line treatment with single EGFR TKI (n=3), combination TKIs (n=3), chemotherapy (n=1), immune checkpoint inhibitors alone (n=1) or in combination with TKI (n=1). In 9 of 9 patients, changes in ctDNA levels from baseline to cycle 2 day 1 on therapy correlated with best response to treatment: a 100% decrease in urine and plasma EGFR mutation levels was observed in 6 of 6 patients with partial response (PR, n=3) or stable disease (SD, n=3), while less than a 90% decrease or an increase in urine and plasma EGFR levels was observed in patients with progressive disease (PD, n=3).
    
    Conclusion:
    Mutation enrichment NGS testing by urine and plasma ctDNA correctly identified EGFR activating mutations in 85% of patients. Monitoring EGFR levels in urine/plasma enabled accurate assessment of response in advance of radiographic evaluation and regardless of therapy type in 100% of patients, with cut-point of a 90% decrease in EGFR load discriminating between patients with disease control (PR or SD) and patients with progressive disease. With continued enrollment, our study aims to further investigate clinical utility of urine and plasma ctDNA for early detection of resistance and discontinuation of inefficient therapy.