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Xiaonan Wang



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-85 - The Prevalence of Different EGFR exon20 Mutations in 12,833 Chinese Lung Cancer Patients (ID 14141)

      16:45 - 18:00  |  Author(s): Xiaonan Wang

      • Abstract
      • Slides

      Background

      Mutations in EGFR exon20 are relatively rare in lung cancers compared to L858R/exon19 mutations, some of which have shown sensitivity to EGFR tyrosine kinase inhibitors (TKIs), and have been actively tested in clinical trials. However, due to the high-variety of EGFR exon20 alterations, it becomes increasingly difficult for their functional studies in related to clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively screened 12,833 Chinese lung cancer patients that have underwent genotyping on their tumor and/or liquid biopsy samples using targeted next-generation sequencing between 2014 and 2017 for EGFR exon20 mutations as well as other concurrent EGFR mutations in the same patient.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 442 patients (3.4%) were found harboring 493 different EGFR exon20 variations, among which 49 patients (11%) carried more than one exon20 mutations. The frequencies of the most prevalent alterations were summarized in Table 1. 18% of these mutations have concurrent TKI-sensitive mutations L858R or exon19 deletion. In-frame deletion/insertions (delins or ins) and missense mutations were identified at a frequency of 53% and 47%, respectively. The short delins/ins occurred between 763~773 residues, while missense mutations dwelled at 768~820 residues, suggesting that these two types of alterations have their own manners for regulating EGFR kinase domain function. The most prevalent insertion is p.M766delinsMASV, occurred in 15.2% of all patients. Meanwhile, the diversity of inserted peptides at p.D770 and p.D771 positions is much higher than other positions with a total of 17 and 19 different insertion peptides composed of 1-5 amino acids, respectively. Missense mutations at S768 were detected in 20.4% of patients, but 60% of them were accompanied by mutations at G719. table 1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the largest cohort of Chinese lung cancers for studying EGFR exon 20 mutations, which should be informative for functional studies, the design of targeted drugs, and the testing for existing therapies.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-24 - EGFR-KDD is Rare and Demonstrates Variable Anti-Tumor Response to Tyrosine Kinase Inhibitors in East Asian NSCLC Population (ID 13253)

      16:45 - 18:00  |  Author(s): Xiaonan Wang

      • Abstract
      • Slides

      Background

      The kinase domain duplication of epidermal growth factor receptor (EGFR-KDD) has been identified and implicated to be oncogenic in non-small cell lung cancer (NSCLC). However, its frequency and clinical outcomes in lung cancer patients are largely uncertain.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a multi-center record review of 8064 East Asian NSCLC patients who underwent genetic testing using next-generation sequencing (NGS) targeting the whole exons of EGFR gene as well as introns involved in EGFR-KDD and gene rearrangements. Patients’ demographic and clinical data, including age, gender, histology type, pathological stage, and their responses to tyrosine kinase inhibitor (TKI) treatments were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      EGFR-KDD was identified in 11 patients, which is approximately 0.012% of the total NSCLC population reviewed (N=8064), and also consists of 0.05% of all patients with EGFR aberrations (N=2289). Nine patients were identified with the canonical EGFR-KDD form involving the duplication of exon 18 throughout exon 25, while the remaining two cases harbor EGFR exon 14-26 and exon 17-25 duplication, respectively, which have not been previously described. Importantly, all these patients were not identified with any other co-existing known driver mutations, highlighting the potential oncogenic role of this alteration. Three out of five patients with exon 18-25 KDD who received TKI treatments showed partial anti-tumor responses to the therapy, while the other two patients progressed shortly. Our data further indicated that EGFR T790M mutation and EGFR amplification may represent the major resistance mechanisms against targeted therapy in tumors bearing EGFR-KDD.

      8eea62084ca7e541d918e823422bd82e Conclusion

      EGFR-KDD is rare in East Asian NSCLC population with different duplication variants. Tyrosine kinase inhibitors demonstrated variable anti-tumor efficacy in patients harboring EGFR-KDD alteration.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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