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Mariano Zalis



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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: 2
    • 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): Mariano Zalis

      • 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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      P2.01-31 - Updated EGFR Mutation Frequency in 1,689 NSCLC Brazilian Patients – A National-Wide Study (ID 14267)

      16:45 - 18:00  |  Author(s): Mariano Zalis

      • Abstract
      • Slides

      Background

      EGFR mutation status is crucial to improving therapeutic results in advanced NSCLC, due to the development of highly effective EGFR-TKIs. Recent local data suggest that EGFR mutation frequency is lower in Brazil ( 22%-33%) than in Asia and higher than in North America and Europe. We intended to describe the EGFR mutation frequency in a large national-wide Brazilian population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This retrospective analysis evaluated a database composed of samples collected between January and August 2017, from all Brazilian regions. Tumor tissue samples of patients with advanced NSCLC were submitted, at discretion of attending physicians, for EGFR mutation testing. EGFR exons 18 to 21 were analyzed by cobas®, NGS, or other non-specified test. Unfortunately, smoking status data was not available and was not included in this analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      1,689 tests were included. Table-1 demonstrates EGFR mutation rates according to test used. Mean age (±SD) was 64.5 (±11.3) for female and 66.0 (±11.1) for male population. From all detected mutations, exon 19 deletion was the most frequent (49.2%), followed by L858R (25.6%), exon 20 insertion (8.4%), T790M (4,7%), and G719X (3.0%). Patients with multiple EGFR variants (more than one EGFR mutation) corresponded to 10.3% of cases. Among different Brazilian geographic macro-regions, EGFRm rate was 33.3% in North (36 tests only), 25.1% in Northeast (307 tests), 30.9% in Central-West (175 tests), 25.8% in Southeast (841 tests), and 20.6% in the South (330 tests) region.

      Table1 – EGFR mutation rate divided by gender and EGFR mutation detection method.

      cobas®

      NGS

      Other

      Overall

      Female

      58/183

      (31.7%)

      223/586

      (38.1%)

      25/159

      (15.7%)

      306/928

      (33.0%)

      Male

      25/167

      (15.0%)

      89/447

      (19.9%)

      9/147

      (6.1%)

      123/761

      (16.2%)

      Overall

      83/350

      (23.7%)

      312/1,033

      (30.2%)

      34/306

      (11.1%)

      429/1689

      (25.4%)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings confirm that EGFR mutation rate among Brazilian is higher than observed in Western countries, women have a higher EGFR mutation rate than men, and detection rate using NGS is higher than cobas®. Frequency of EGFR mutation was lower in South region, what could be explained by a higher smoking rate (not evaluated in this study) and a larger Caucasian population.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.