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Ming Yao



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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-07 - Co-Occurring Genomic Alterations in EGFR Altered Chinese Lung Adenocarcinoma Patients (ID 14340)

      12:00 - 13:30  |  Author(s): Ming Yao

      • Abstract

      Background

      EGFR mutation is one of the most common driver gene mutations in non-small cell lung cancer (NSCLC) patients, especially in adenocarcinoma. Increasing numbers of rare alterations of EGFR such as kinase domain duplication and fusion have been identified with the clinical applications of next generation sequencing (NGS). However, co-occurring genomic alterations of EGFR have not been fully understood in Chinese lung adenocarcinoma patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      FFPE tumor and matched blood samples of 989 Chinese patients with confirmed histology subtype of adenocarcinoma, consisting of 503 males and 486 females with a median age of 60 years, were collected for NGS-based 450 cancer genes panel assay. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indel), copy number variations (CNV) and gene rearrangements in selected genes were assessed.

      4c3880bb027f159e801041b1021e88e8 Result

      About 57% of Chinese lung adenocarcinoma patients harbored at least one EGFR genomic alteration, which was mainly composed of patient with SNVs and Indels (74%), both gene amplifications and SNVs/Indels (23%), gene amplifications only (2.7%) and gene rearrangements (0.5%). 20% of the patients with SNVs and Indels in EGFR carried more than one EGFR mutations. Moreover, EGFR gene rearrangement was mutually exclusive with other types of genomic alterations.

      Exon 19 deletions and L858R substitution were the most common EGFR mutations, which accounted for 37.9% and 33.7% of all EGFR alterations, respectively. Exon 20 insertions, the mostly insensitive variant to EGFR-TKIs, amounted to 3.7%, and the most common resistant alteration T790M accounted for 5.9%. Uncommon EGFR mutations including L861Q, G719X, S768I and others were identified in 18.9% of patients with EGFR mutations.

      Further analysis of co-occurring EGFR mutations and kinase receptor fusions revealed that 1.1% (6 of 559) of EGFR mutated Chinese NSCLC patients harbored both EGFR mutations and known druggable kinase receptor fusions including ROS1, RET and NTRK. Three of the six patients received EGFR-TKI as the standard treatment. One patient achieved partial response for 10 months and two achieved stable disease for 5 and 4 months, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      About 38% of Chinese lung adenocarcinoma patients harbored more than one EGFR genomic alterations, and 19% of EGFR mutations identified in Chinese lung adenocarcinoma patients were uncommon mutations. In addition, 1.1% of EGFR mutated patients also harbored known druggable kinase receptor fusions. Though our preliminary data showed that the co-existence of EGFR mutations and kinase receptor fusions might be associated with shorter response time to EGFR-TKIs, further large cohort study is needed to validate this finding.

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    P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.12-14 - Genomic Profiling of Chinese Small Cell Lung Cancer and the Implications for Therapy (ID 14425)

      12:00 - 13:30  |  Author(s): Ming Yao

      • Abstract

      Background

      Small cell lung cancer (SCLC) is one of the deadliest malignancies and accounts for nearly 15% of lung cancers. The 5-year survival rate for SCLC is very low. Previous study had revealed the genomic characterization of SCLC in Western patients. However, little is known about that in Chinese SCLC patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      FFPE tumor and matched blood samples of 79 Chinese SCLC patients, including 60 males (median age of 60 years old) and 19 females (median age of 59 years old), were collected for next generation sequencing to detect 450 cancer related genes. All histological diagnoses were confirmed by independent pathologists. Genomic alterations including single nucleotide substitutions (SNV), short and long insertions/deletions (Indel), copy number variations (CNV), and gene rearrangement in selected genes were assessed.

      4c3880bb027f159e801041b1021e88e8 Result

      The most frequently altered genes in 79 Chinese SCLC patients were TP53 (94.9%), RB1 (83.5%), LRP1B (22.8%), KMT2D (13.9%), NOTCH1 (12.7%), FAM135B (11.4%), FAT1 (11.4%), KDR (11.4%), SPTA1 (10.1%) and STK24 (10.1%). Four of the patients harbored EGFR alterations including one EGFR fusion. Copy number variation analysis revealed that the most frequent variations occurred in the long arm of chromosome 13, including amplifications of STK24, FGF14, IRS2 and TNFSF13B (10.1%, 8/79, located at 13q32~13q34) and deletion of RB1 and BRCA2 (59.5%, 47/79, located at 13q13~13q14). Compared to the previously reported 25% mutational frequency in Western cohort reported previously, 31.6% (25/79) of our patients exhibited alterations in NOTCH signaling pathway related genes (NOTCH1, NOTCH2, NOTCH3, NOTCH4, EP300 and CREBBP). Around 15.2% (12/79) patients had PI3K/AKT/mTOR signaling pathway alterations (PIK3CA, MTOR, PTEN, and TSC2). Homologous Recombination Deficiency (HRD) related genes altered in 17.7% (14/79) patients, suggesting the potential clinical benefits from PARP inhibitors. The genomic alterations of FGF family members occurred in 25.3% (20/79) of patients. Other targetable genes included KIT (7.6%, n = 6), PDGFRA (5.1%, n = 4) and DDR2 (2.5%, n = 2).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this study, we characterized the genomic alteration profile of Chinese SCLC patients. Our discovery of CNV in the long arm of chromosome 13 might be helpful in understanding the pathogenesis of SCLC. Consistent with previous report, high mutation rates of TP53 and RB1 are the most important genomic features of SCLC [PMID: 26168399]. In addition, we also found several targetable gene variations including HRD, FGF family, KIT, PDGFRA and DDR2, which might provide potential targeted therapy options for SCLC patients. Further association analyses of these genomic alterations with clinical features in SCLC are still needed.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.13-21 - Apatinib Plus Icotinib as First-Line Therapy For EGFR Co-Mutations NSCLC in Chinese Patients: An Exploratory Study (ID 11987)

      12:00 - 13:30  |  Author(s): Ming Yao

      • Abstract

      Background

      To date, the phenomenon of EGFR co-mutated with other genes in untreated NSCLC patients was common, which might be the reason of EGFR-TKI primary resistance. In our previous research, samples from 81 NSCLC Chinese patients were tested with next-generation sequencing (NGS) based targeted panel assay, 49% (40/81) patients had EGFR co-mutations´╝îthe top-ranked co-mutant genes were TP53 (35%, 28/81) and cell cycle pathway related genes (19%, 15/81). Clinical data indicated that antiangiogenic drug combination with EGFR-TKI might reverse EGFR-TKI acquired resistance. Apatinib is a new antiangiogenic drug targeting vascular endothelial growth factor receptor 2 (VEGFR2), and Icotinib is a potent and specific EGFR-TKI, which were both made in China. In this study, we aim to assess the efficacy and safety of Apatinib plus Icotinib as first-line therapy for EGFR co-mutations NSCLC in Chinese patients, and compare the differences of curative effect among EGFR co-mutant subgroups.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This single-arm, open-label exploratory study will recruit 50 Chinese patients with stage IIIB/IV NSCLC who have never received any anti-tumor treatment previously. Tumor tissue and matched blood of each patient will be collected for NGS-based 450 cancer related genes panel assay, designed to comprehensively assess EGFR mutation and co-mutations. Meanwhile, ctDNA extracted from blood samples will be collected for NGS-based 329 cancer related gene before treatment as baseline, and every 2 months after enrollment until disease progression, to evaluate the evolution of genomic variation and effects of drug efficacy. The analysis of genomic alterations including single base substitution, short and long insertions/deletions, copy number variations, gene rearrangement in selected genes and also tumor mutation burden (TMB) calculated as total somatic substitutions and indels per megabase. Patients with EGFR-sensitizing mutations accompanied with other genomic alterations will receive Apatinib 250mg, qd, po and Icotinib 150mg, tid, po until disease progression, or unacceptable toxicity. The primary endpoint of this study is progression free survival (PFS), and the secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality of life (QOL) and drug-safety.

      4c3880bb027f159e801041b1021e88e8 Result

      Not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Not applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53