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C. Pallarés

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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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      P1.06-043 - Pharmacogenetic study in advanced non-small cell lung cancer patients treated with platinum based chemotherapy. (ID 2698)

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

      • Abstract

      Platinum-based doublet chemotherapy (CT) is the standard treatment in non-small cell lung cancer (NSCLC) patients, but less than 30% respond to CT, and survival remains between 10-12% at five years. The most important prognostic factor in survival is the stage, although there is significant variability in survival among patients with similar disease. It is postulated that different single nucleotide polymorphisms (SNPs) in DNA repair genes may play a role in the effectiveness of the platinum-based chemotherapy. The purpose of this study was to evaluate the association of 17 SNPs in 8 genes involved in DNA repair mechanisms, with the response to treatment with platinum-based chemotherapy in NSCLC patients.

      The genomic DNA was automatically extracted from blood samples using the salting out procedure (Autopure, Qiagen) and was quantified using the BioSpec-nano spectrophotometer. We analyzed 17 polymorphisms belonging to 8 genes, using 48.48 dynamic array on the Biomark™ system (Fluidigm): six genes belong to the Nucleotide Excision Repair pathway (ERCC1, ERCC2/XPD, ERCC3/XPB, ERCC4/XPF, ERCC5/XPG and XPA), and two genes belong to the Base Excision Repair pathway (XRCC1, XRCC2).

      We included 161 patients with stage IIIA-IV. The median age was 63.7 years; 77.6% were men, and 54% had stage IV disease. All patients received a platinum agent (cisplatin: 95, carboplatin: 66) in combination with a third-generation drug. Patients with stage IIIA and IIIB also received concomitant or sequential radiotherapy. In patients with stage IIIA and IIIB (n=74), the multivariate analyses showed a significant association between the following SNPs and response: rs11615 (ERCC1) (p=0.0448 in a recessive model), rs3738948 (ERCC3) (p=0,0049 in an additive model). In patients with stage IV (n=87), the multivariate analyses showed a significant association between the following SNPs and response: rs1799793 (ERCC2) (p=0.013 in a recessive model), rs179801 (ERCC4) (p=0.033 in a dominant model) and rs25487 (XRCC1) (p=0.002 in a recessive model).

      These results confirm the association between polymorphisms in genes ERCC1, ERCC2 and XRCC1 and response to treatment with platinum compounds as previously described. In our cohort, response to treatment was also associated with genes ERCC3, ERCC4, also involved in DNA repair processes. Prospective studies are needed in order to validate the role of polymorphisms as predictors of response to chemotherapy in NSCLC patients.