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C. Zhao



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    MINI 13 - Genetic Alterations and Testing (ID 120)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI13.12 - The Abundance of EGFR Mutations Could Be More Better Predictor for EGFR-TKI Therapy in Advanced Non-Small Cell Lung Cancer (ID 1481)

      10:45 - 12:15  |  Author(s): C. Zhao

      • Abstract
      • Presentation
      • Slides

      Background:
      Incresing data show advanced non-small cell lung cancer (NSCLC) patients with EGFR activating mutant have discrepant response to EGFR-TKI. The abundance of EGFR mutations may be a powerful explanation for the uneven clinical benefit. This study was designed to investigate the influence of EGFR mutant abundance on efficacy of EGFR-TKI by a quantitative method.

      Methods:
      201 NSCLC patients treated with EGFR-TKI with available tissue samples for EGFR mutation test were enrolled into the study. EGFR common mutations were detected by amplification refractory mutation system (ARMS) and percentage of mutant EGFR was tested with the method of an Allele Specific Quantitative PCR with Competitive Blocker (ASB-qPCR). In this assay, the copies of all mutations and EGFR locus were calculated by standard curve respectively. The cutoff values were obtained by the receiver operating characteristics (ROC) curve in training set. Further, the cutoff values were confirmed in validation set and the whole population. The relationship between the abundance of EGFR mutations and efficacy of EGFR-TKI was statistically analyzed.

      Results:
      Of the 201 samples, 72 harbored 19DEL mutation, 63 carried L858R mutant, and 66 with wild-type. The cohort was randomly divided into training and validation sets. The cutoff values of 19DEL and L858R mutation abundance were 4.84% and 9.47% determined by ROC curve in training set. 9.7% of patients with 19DEL positive were low abundance (<4.84%, LA group), while 33.3% of L858R-positive patients were LA (<9.47%).High abundance (HA) group, regardless of 19DEL or L858R positive had more longer median progression free survival (PFS) compared with LA and wild-type groups in either validation set or the whole population (15.0 vs 2.0 vs 1.9, 8.0 vs 1.9 vs 1.9; 15.0 vs 4.0 vs 2.0, 12.0 vs 2.0 vs 2.0; p<0.001). COX regression analysis showed that EGFR mutation abundance, together with smoking status, were independent factors of response to EGFR-TKI.

      Conclusion:
      The abundance of EGFR mutation could more precisely predict EGFR-TKI efficacy. NSCLC patients with LA mutation had inferior clinical benefit with EGFR-TKI. The heterogeneity in EGFR mutant abundance partly explain the efficacy discrepancy in patients with 19DEL or L858R positive.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-049 - HER-2 Mutations in Chinese Lung Adenocarcinoma Patients with Negative EGFR Mutations (ID 1345)

      09:30 - 17:00  |  Author(s): C. Zhao

      • Abstract

      Background:
      To determine the prevalence and clinicopathological features of epidermal growth factor receptor 2 (HER-2) mutations in Chinese lung adenocarcinoma patients with negative EGFR mutations.

      Methods:
      Formalin-fixed and paraffin-embedded (FFPE) tissue sections from 398 lung adenocarcinoma patients with wild-type EGFR were screened for HER-2 mutations by amplification refractory mutation system (ARMS) assay and all HER-2 mutations were validated by direct sequencing. The protein expression of HER-2 was evaluated by immunohistochemistry (IHC). Of the 398 samples, 331 were also detected ALK and ROS1 fusions by multiplex RT-PCR, and all fusions positive were verified by direct sequencing. The relationship between HER-2 mutations and clincopathological features and the prognostic effect of its status on disease free survival (DFS) were analyzed.

      Results:
      21 of 398 (5.3%) harbored HER-2 mutations; 7.6% of 278 samples with triple-negative lung adenocarcinoma ( EGFR-, ALK-, ROS1-) were found to have HER-2 mutations. 17 samples (81.0%) were A775_G776insYVMA, two with G776>VC, one with V777_G778insGSP and the last one with 2340_2341ins12 in-frame insertions of exon 20. 59 of 398 (14.8%) were positive of HER-2 expression. No association was found between HER-2 mutations and expression, only two patients coexisted the positive in mutation and expression. There was no statistically significant difference in age, sex, smoking history, and pathological stage between patients with HER-2 mutations and those with negative patients. The DFS of patients with HER-2 mutations have no significant difference compared with those patients with negative mutations.

      Conclusion:
      5.3% of Chinese lung adenocarcinoma with wild-type EGFR harbored HER-2 mutations. The HER-2 mutations had no association with HER-2 expression.