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C. Chamizo

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-035 - VEGF-A 165 family of isoforms as predictive biomarkers in patients with non-squamous non-small cell lung cancer (NSCLC) treated with bevacizumab. (ID 2450)

      09:30 - 16:30  |  Author(s): C. Chamizo

      • Abstract

      Bevacizumab is a recombinant monoclonal humanized antibody targeted against vascular endothelial growth factor (VEGF) that improves Time to Progression (TTP) in patients with advanced non-squamous NSCLC in combination with a doublet of platins, but currently no proven predictive markers exist. The VEGF-A 165 splice variant has been described as the most abundant and active isoform in cancer. Exon 8 distal splice site modifications of VEGF 165 generates the VEGF-A 165a family of isoforms, which has a pro-angiogenic effect, and the VEGF-A 165b family, with an anti-angiogenic activity in in vivo models. This study is aimed to explore the role of VEGF165a and VEGF165b isoform expression in tumors as predictive biomarkers of efficacy in patients with non-squamous NSCLC treated with a doublet of platin plus bevacizumab.

      22 patients were included (20 adenocarcinomas and 2 large cell carcinomas): 5 received carboplatin-taxol-bevacizumab, 14 carboplatin-taxotere-bevacizumab and 3 cisplatin-gemcitabine-bevacizumab. Total RNA was isolated from clinical samples by RNeasy FFPE procedure (Qiagen). VEGF~165~a and VEGF~165~b expression was analyzed by RT-qPCR using appropriate specific primers and probes in LightCycler 480II platform at 45 cycles. Individual VEGF~165~a and VEGF~165~b family of isoforms expression was calibrated to normal tissue and the ratio between both isoforms was calculated.

      From studied cases, VEGF~165~a overexpression was detected in 14 (63.6%) cases and VEGF~165~b overexpression in 15 (68.2%) tumors. Individual overexpression for each family of isoforms was not predictive of benefit to bevacizumab therapy (p=0.933 and 0.166). However, the ratio between VEGF~165~a and VEGF~165~b was associated with TTP, correlating a predominant expression of the pro-angiogenic VEGF~165~a in tumor with a significant benefit compared with cases with predominant VEGF~165~b expression (median TTP, 15 vs. 8 months respectively, p=0.005). The expression of both family isoforms did not impact on overall survival (p=0.477).

      The overexpression of VEGF~165~a family of isoforms associated with a low expression of VEGF~165~b correlated with benefit to anti-angiogenic therapy in this small cohort of advanced NSCLC patients, supporting a potential use as predictive biomarkers for bevacizumab treatment in stage IV non-squamous NSCLC.