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I.D.C. Werneck



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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.02-060 - EGFR Mutation Status by Three Sequencing Platforms in 704 Non-Small Cell Lung Cancer (NSCLC) Brazilian Patients (ID 10371)

      09:30 - 09:30  |  Author(s): I.D.C. Werneck

      • Abstract
      • Slides

      Background:
      EGFR status has utmost importance in treatment of NSCLC with the emergence of highly effective anti-EGFR tyrosine-kinase inhibitors (TKI). Current technologies for EGFR evaluation are based on sequencing platforms, such as Sanger, Pyrosequencing (Pyro) and Next Generation Sequencing (NGS), used in different timeframes during the last 6 years of our local practice. Indirect evidence demonstrates that Latin American patients have higher frequency of EGFR mutations. We aimed to describe EGFR mutation frequency in a Brazilian population and concordance of findings and differences between available sequencing techniques.

      Method:
      Between August/2010-July/2016 we performed a retrospective analysis of the reports of formalin-fixed paraffin-embedded 704 consecutive biopsy samples from TKI-naïve patients tested for EGFR at A.C.Camargo Cancer Center, São Paulo, Brazil. EGFR exons 18 to 21 were analyzed by Sanger, Pyro or NGS. All tests were performed locally.

      Result:
      EGFR mutation aggregated rate was 26.7% for the overall population. Table 1 shows patient’s characteristics (when medical records were available) including differences between mutated and non-mutated patients. Table 2 demonstrates differences between mutation findings for each sequencing platform.

      Table 1. Patient Characteristics. WT: Wild Type. Mut: Mutant.
      WT EGFR Mut EGFR P value
      GENDER
      Male 223/516 (43.2%) 63/188 (33.5%)
      Female 293/516 (56.8%) 125/188 (66.5%) <0.001
      MEDIAN AGE AT DIAGNOSIS (YEARS) 64 64.8 0.72
      HISTOLOGY
      Adenocarcinoma 367/418 (87.8%) 156/161 (96.9%)
      Non-Adenocarcinoma NSCLC 51/418 (12.2%) 5/161 (3.1%) 0.01
      SMOKING STATUS
      Nonsmoker 81/308 (26.3%) 52/128 (40.6%)
      Smoker/Former Smoker 227/308 (73.7%) 76/128 (59.4%) < 0.001
      MEDIAN SMOKING LOAD (PACK-YEARS) 40 17.5 < 0.001
      METASTASIS AT DIAGNOSIS
      Yes 238/333 (71.5%) 105/137 (76.6%)
      No 95/333 (28.5%) 32/137 (23.4%) 0.25
      Table 2 – Numbers and types of mutations detected according to the test methodology.
      Sanger Pyro NGS Aggregated
      EGFR Mutant Patients 82/352 (23.3%) 27/101 (26.7%) 79/251 (31.5%) 188/704 (26.7%)
      Total Number of EGFR Variants Detected* 93 28 84 205
      Patients with Multiple EGFR Variants 8/82 (9.8%) 1/27 (3.7%) 5/79 (6.3%) 14/188 (7.4%)
      Sensitivity Variants 69/93 (74.5%) 26/28 (92.9%) 71/84 (84.5%) 166/205 (81%)
      Resistance Variants 3/93 (3.2%) 0 6/84 (7.1%) 9/205 (4.4%)
      Variants of Uncertain Significance 21/93 (22.6%) 2/28 (7.1%) 7/84 (8.3%) 30/205 (14.6%)
      Inconclusive test 60/352 (17%) 4/101 (4%) 5/251 (2%) 69/704 (9.8%)


      Conclusion:
      Our findings demonstrate higher than expected EGFR mutation rate among for caucasian patients in a Brazilian population and a numerically higher and broader EGFR mutation detection rate with NGS.

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