Author of

• 16051

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  ORAL 42 - Drug Resistance (ID 160)

  • Event: WCLC 2015
  • Type: Oral Session
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:R.C. Doebele, J.V. DeGregori
  • Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 4a-4f

  • 16056

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    ORAL42.05 - <em>SMARCA4</em>/BRG1 Is a Biomarker for Predicting Efficacy of Cisplatin-Based Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) (ID 849)

    19:13 - 19:24  |  Author(s): M. McNulty
    • Abstract
    • Slides

    Background:
    Adjuvant platinum-based chemotherapy remains a primary treatment of non-small-cell lung cancer (NSCLC); however, identification of predictive biomarkers is critically needed to improve the selection of patients who derive the most benefit. In this study, we hypothesized that decreased expression of SMARCA4/BRG1, a known regulator of transcription and DNA repair, is a predictive biomarker of increased sensitivity to platinum-based therapies in NSCLC. Moreover, this study also sought to confirm the prognostic role of SMARCA4/BRG1 in NSCLC.
    
    Methods:
    The prognostic value of SMARCA4 expression levels was tested using a microarray dataset from the Director’s Challenge Lung Study (n=440). Its predictive significance was determined using a gene expression microarray dataset (n=133) from the JBR.10 trial, and RT-PCR data from 69 patients enrolled on the MADe-IT trial and 33 platinum-treated patients from an institutional cohort.
    
    Results:
    In the Director's challenge study, low expression of SMARCA4 was found to be associated with poor overall survival compared to high and intermediate expression (P = 0.006). Upon multivariate analysis, compared to high, low SMARCA4 expression predicted an increased risk of death and confirmed its prognostic significance (HR=1.75; P=0.002). In the JBR.10 trial, improved five-year disease-specific survival was noted only in patients with low SMARCA4 expression when treated with adjuvant cisplatin/vinorelbine (HR 0.1, P= 0.001 (low); HR 1.1 , P= 0.762 (high)). An interaction test showed significance (P=0.007). In addition, a trend toward improved progression-free survival was noted only in patients with low SMARCA4 receiving a carboplatin- versus a non-carboplatin-based regimen in the MADe-IT trial. Figure 1 Fig1. Low SMARCA4 correlates with improved disease-specific survival with adjuvant cisplatin-based chemotherapy in the JBR.10 trial.
    
    
    
    Conclusion:
    Although decreased expression of SMARCA4/BRG1 is significantly associated with worse prognosis, it is a novel significant predictive biomarker for increased sensitivity to platinum-based chemotherapy in NSCLC patients.
    
    

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