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Tal Twito



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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-28 - The Clinical Impact of Comprehensive cfDNA Genomic Testing in Lung Cancer (ID 13878)

      12:00 - 13:30  |  Author(s): Tal Twito

      • Abstract

      Background

      Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables a non-invasive option for comprehensive genomic analysis of non-small cell lung cancer (NSCLC) patients. Although plasma-detected genomic alterations have been shown to predict targeted therapy response, evidence of durability of response is lacking or limited to small cohorts as is the impact of cfDNA NGS results on clinical decision making.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this retrospective study, data was collected on stage IIIB/IV NSCLC patients between the years 2014-2017 in Israel. We utilized cfDNA NGS (Guardant360) which covers the seven genes targetable with FDA-approved therapies in NSCLC.

      4c3880bb027f159e801041b1021e88e8 Result

      116 consecutively NSCLC patients were tested, 41.4% (48/116) before 1st line therapy (Group A), 34.5% (40/116) upon progression on chemotherapy or immunotherapy (Group B1) and 24.1% (28/116) upon progression on EGFR TKIs (Group B2). Targetable genomic alterations were found in 65% of group A (15/48), 53% in group B1 (21/40) and 71% in group B2 (20/28). Treatment decision was changed to targeted therapy based on cfDNA NGS analysis in 23% (11/48), 25% (10/40) and 32% (9/28), respectively (total cohort 26%; 30/116). Response assessment (RECIST) showed complete response in 4% (1/28), partial response in 39% (11/28), stable disease in 32% (9/28) and progressive disease in 25% (7/28). Total objective response rate (ORR) was 43% and disease control rate was 75% for 5 months treatment duration.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Comprehensive cfDNA testing impacted clinical decisions in 23% of naïve patients, 25% in patients who progressed on chemotherapy and 32% in EGFR TKI progressors. Median treatment duration was 5 months. This retrospective study extends previous reports by showing that responses based on cfDNA are durable and change treatment decisions at initial presentation and at progression.

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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-11 - The Influence of Circulating Tumor DNA Analysis on Response to Immunotherapy in Non-Small Cell Lung Cancer (NSCLC) (ID 13810)

      12:00 - 13:30  |  Author(s): Tal Twito

      • Abstract
      • Slides

      Background

      In advanced NSCLC, immunotherapy has demonstrated good response rates with some responses being remarkably durable, however emerging biomarkers predictive of response (or lack thereof) include PD-L1 expression, tumor mutation burden (TMB), genomic alterations in EGFR/ALK/ROS1 and KRAS/TP53/STK11 mutations, all competing for limited tissue biopsy samples. Therefore, we investigated whether these biomarkers can be detected from a non-invasive plasma sample. In particular, challenges to assessment of TMB with cell-free DNA next-generation sequencing (NGS) include the limited size of liquid biopsy gene panels and the fact that low shedding of tumor DNA into circulation may fail to detect hypermutated tumors. We previously reported, in a modest 27 advanced NSCLC cohort, that TMB can be ascertained with a 73-gene cfDNA NGS panel that adjusts for the degree of tumor shedding, and here investigate whether detection of TMB and the above genomic mutations can be used to predict immune checkpoint inhibitor response in a larger cohort.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this retrospective study, data were collected on NSCLC patients treated in multiple medical centers in Israel between 2014 and 2017. We used NGS on cell-free circulating tumor DNA (ctDNA) to evaluate whether mutational burden and specific genomic alterations influence the response to immunotherapy in these patients.

      4c3880bb027f159e801041b1021e88e8 Result

      Overall, 336 NSCLC patients underwent NGS on ctDNA. Of these 336 patients, 192 (57%) were females and 144 (43%) were males. The average age (range) was 64 (23-103) years. Clinical treatment information is currently available for 117 patients, of whom 50 (43%) received immune check-point inhibitors. Rates of stable disease, partial and complete responses (RECIST criteria), as well as progression-free survival and overall survival will be reported. In addition, to unravel the genomic determinants of response to immunotherapy we will use the blood-derived ctDNA to understand if hypermutated ctDNA is a predictive biomarker of response to immunotherapy.

      8eea62084ca7e541d918e823422bd82e Conclusion

      ctDNA collection was feasible in 336 patients. A prediction model to associate the ctDNA signature with response to immunotherapy based on plasma will be presented.

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