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Bruna Silva



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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-128 - Low Positivity Rate in T790M Detection with ctDNA in NSCLC and Post EGFR-TKI Progression – Timing or Sensitivity? (ID 14293)

      16:45 - 18:00  |  Author(s): Bruna Silva

      • Abstract
      • Slides

      Background

      The approval of Osimertinib in Brazil in 2016 for post EGFR-TKI progression T790M+ NSCLC treatment allowed offering to the patient the best available therapy, when, it is mandatory to identify the occurrence of T790M mutation before initiating the treatment. The prevalence of T790M mutation as resistance mechanism post EGFR-TKI treatment is estimated to be around 60%. Considering the limitations for tumor tissue biopsy in progressive disease setting, identifying molecular changes by using alternative tumor DNA sources, such as blood samples, serum, and plasma can become an interesting strategy in cases where a tissue specimen or acceptable quality biopsy is not available. However, the sensitivity of ctDNA analysis for T790M may be disappointingly low.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a retrospective analysis of ctDNA samples database collected between June 2016 and December 2017 in Brazil. Blood samples of patients with post EGFR-TKI progression were submitted, at discretion of attending physicians, for EGFR mutation testing by cobas®.

      4c3880bb027f159e801041b1021e88e8 Result

      761 tests were included. The positivity rate was 43.9% for EGFRm and 10.4% for T790M. Considering EGFRm positive tests, the positivity rate for T790M among EGFRm positive was 23.7%. Data are shown in Table-1. This positive rate is lower than expected and may be explained by three factors: T790M ctDNA cobas® low sensitivity; test request before progression; or T790M prevalence lower in Brazilian population. Still, more detailed testing using tissue and/or more sensitive methods are needed before definitive conclusion. Tissue test should continue being recommended as gold standard in T790M detection on this patient setting.

      Table 1- Frequency and mutations detected by ctDNA cobas® test in Brazil.

      Exon

      18

      19

      20

      21

      19 + 20

      21 + 20

      Mutation

      G719X

      19Del

      19Ins

      T790M

      L858R

      L861Q

      19Del + T790M

      L858R

      +

      T790M

      Number

      9

      183

      1

      9

      60

      2

      53

      17

      Positivity rate (%)

      1.2

      24.1

      0.1

      1.2

      7.9

      0.3

      7.0

      2.2

      % of EGFRm

      2.7

      54.8

      0.3

      2.7

      18.0

      0.6

      15.9

      5.1

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings suggest that ctDNA approach in post EGFR-TKI progression may not be the best diagnostic strategy to identify resistance T790M mutation as first option. When patient cannot be submitted to tissue biopsy at progression, ctDNA test is an acceptable alternative.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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