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Hong Shi



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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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      P2.01-117 - Concurrent Gene Alterations in Treatment-Naïve EGFR-Mutant Advanced Non-Small Cell Lung Cancer (ID 13102)

      16:45 - 18:00  |  Author(s): Hong Shi

      • Abstract
      • Slides

      Background

      EGFR-TKIs is the standard first line treatment for EGFR-mutant advanced non-small-cell lung cancer (NSCLC). However, 20% to 30% of patients who receive EGFR-TKIs exhibit primary resistance. The gene alterations in treatment-naïve EGFR-mutant advanced NSCLC should be better explored.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed gene test results of 980 treatment-naïve advanced NSCLC samples in our institute. Tumor biopsy, ctDNA, pleural effusion or cerebrospinal fluid samples were analyzed using hybridization capture-based NGS ER-seq method, white blood cells as control, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number(CNV) variation at least 59 genes (range 59-1021 genes).

      4c3880bb027f159e801041b1021e88e8 Result

      Three hundreds and eighty one cases with EGFR sensitive mutation were identified, 358 adenocarcinoma, 7 squamous cell carcinoma, 1 adenosquamous carcinoma and 15 NSCLC. Among the patients, 88 patients (23.1%) harbored concurrent actionable mutations with EGFR, which 43 were exon 19 deletion, 37 were L858R and 8 were uncommon EGFR mutations. One patient had co-occurring L858R, T790M and CDKN2A frameshift mutation. The actionable mutations were from 23 genes, which involved in cellular signaling pathways, and some genes had been reported associated with EGFR-TKIs resistance (details in table). Except the actionable mutations, TP53 mutations were detected in 225 samples (59.1%, 225/381), which 35.1% (79/225) in exon8. Bcl-2–like 11(BIM) deletion were detected in 31 (8.1%, 31/381) white blood cells.

      Signaling Pathways

      Concurrent gene alterations

      Frequency(N=88)

      Cell cycle*

      CDKN2A

      3.9%

      CDK4

      2.1%

      CCNE1

      0.8%

      CCND1

      0.8%

      CCND3

      0.3%

      PI3K/AKT/mTOR*

      PIK3CA

      2.9%

      PTEN

      1.3%

      TSC1/2

      1.0%

      AKT2

      0.3%

      NF1

      0.3%

      RTKs*

      MET

      0.8%

      HER2

      0.8%

      FGFR2

      0.3%

      FGFR3-TACC3

      0.3%

      Ras/Raf/MAPK*

      KRAS

      0.8%

      Homologous Recombination Repair pathway

      BRCA2(sc+gm)

      0.8%

      BRCA1(sc)

      0.5%

      ATM

      0.5%

      PALB2

      0.3%

      Others

      CTNNB1

      2.9%

      MDM2

      2.4%

      SMARCA4

      0.8%

      JAK2

      0.5%

      sc, somatic mutation;

      gm, germline mutation;

      *, genes had been reported associated with EGFR-TKIs resistance

      8eea62084ca7e541d918e823422bd82e Conclusion

      Concurrent gene alterations in treatment-naïve EGFR-mutant advanced NSCLC is common, and mutiple genes are involved. This maybe contribute to the primary resistance to EGFR-TKIs in EGFR-mutant advanced NSCLC. Indicate the importance of multiplex molecular test and further researches of target therapies.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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