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Liming Cao



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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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      P1.01-61 - Clinical Characterization of ERBB2 Exon 20 Insertions and Heterogeneity of Outcomes to Afatinib in Chinese Lung Cancers (ID 13066)

      16:45 - 18:00  |  Author(s): Liming Cao

      • Abstract
      • Slides

      Background

      Background: Human epidermal growth factor 2 (HER2, ERBB2) gene alterations have been identified as oncogenic drivers in 2-5% of lung cancers. ERBB2 In-frame insertions in exon 20 (20ins) lead to constitutive activation of receptor and downstream pathways. However, response heterogeneity of different exon 20 insertions to ERBB2 inhibitor afatinib exists. In vitro and structural modeling results suggested that Glycine778 may facilitate inhibitor binding to ERBB2. In this study, our aim was to improve our understanding of clinical characteristics in ERBB2-mutated Chinese lung cancer and investigate the clinical outcomes of specific ERBB2 exon 20 insertions in response to afatinib.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods: We reviewed 7520 lung cancer patients whose tissue or plasma biopsies were sequenced in a CLIA-certified sequencing laboratory between 2015 to 2018. Clinical records of 19 patients (18 adenocarcinomas and 1 squamous cell carcinoma) with several different ERBB2 20ins after afatinib treatment were collected for clinical outcomes evaluation.

      4c3880bb027f159e801041b1021e88e8 Result

      Results: ERBB2 20ins were identified in 2.27% (171/7,520) in this Chinese lung cancer cohort. It occurred with a high proportion in females with adenocarcinoma histology. 11.7% (20/171) ERBB2 20ins-positive patients harbored concomitant ERBB2 amplification. Y772_A775dup (119/171, 69.6%) was the most frequently occurred 20ins subtype, followed by G778_P780dup (18/171, 10.5%). For the 19 patients treated with afatinib, they had a median PFS of 4.5 months and median OS of 11.5 months. The overall response rate in this cohort was 15.8% (3/19) and disease control rate was 68.4% (13/19). Next, we interrogated the clinical outcomes of specific 20ins subtype responding to afatinib. We found that patients harboring G778_P780dup (G778) achieved longer median PFS (10 vs 3.3 months, p=0.32) and median OS (19.7 vs 7 months, p=0.16) than non-G778 patients, consisting with in vitro results. Although statistical significance was not achieved due to limited number of G778_P780dup patients, this result warranted further investigation into this phenomenon. Moreover, to the best of our knowledge, we identified the first case of a lung squamous cell carcinoma patient harboring ERBB2 20ins from this cohort. He displayed favorable response to afatinib and achieved partial response with significant tumor shrinkage.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusion: We interrogated the characteristics of ERBB2 exon 20 insertions in a large cohort from single ethnicity. It demonstrated the response heterogeneity to afatinib among different ERBB2 exon 20 insertion subtypes. It highlighted the importance to correlate drug efficacy with specific ERBB2 exon 20 insertion variants in clinical application.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.03 - Biology (Not CME Accredited Session) (ID 935)

    • 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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      P1.03-11 - Analysis of T-Cell Repertoires in Benign and Malignant Solitary Pulmonary Nodules to Evaluate Tumor Immune Microenviroment (ID 13175)

      16:45 - 18:00  |  Author(s): Liming Cao

      • Abstract
      • Slides

      Background

      The identification of malignancy of solitary pulmonary nodule (SPN) is important for lung cancer eraly detection. Carcinogenesis may result from accumulation of molecular evolution and escaping from host immunoediting. However, the immune landscape such as T cell repertoire of benign and malignant SPNs have not been systemically studied.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We have collected resected solitary pulmonary nodules (SPNs) and peripheral blood including benign SPNs (N=10), LUSC (N=11) and LUAD (N=38) from
59 patients. T cell repertoire of infiltrating T cells in SPNs were sequenced their T cell receptor b genes (TCRb) , as well as their abundance in peripheral blood. Enrichment clonotypes were defined as 500 fold enrichment as compared to blood.

      4c3880bb027f159e801041b1021e88e8 Result

      Comparison to the peripheral blood, T cell repertoire diversity of infiltrating T cells in SPNs showed significant differences among benign and malignant. T cell clonality was higher in the benign SPNs than Malignant, however no significant differences among LUSC and LUAD. Additionally, we observed that Tumors from smokers had higher T cell clonality than no-smokers as reported earlier. Interestingly, many T cell clones, including major clones, were shared between lung tissues and matched peripheral blood; furthermore, the higher shared clonotypes of T cell clones between lung tissues and blood in benign SPNs than Malignant. Enrichment analysis demonstrated more enriched clonotypes observed in LUSC and LUAD.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our preliminary data demonstrate the distinct immune microenvironment in SPNs may be associated with the benign and malignant features. And implies a significant proportion of infiltrating T cells in SPNs may be a function of constant lung infiltrating rather than an anti-tumor response.

      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.