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  P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

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    P3.06-051 - Circulating biomarkers may help guide selection of erlotinib versus chemotherapy in pretreated advanced NSCLC patients. (ID 3364)

    09:30 - 09:30  |  Author(s): J.A. Gangaram
    • Abstract

    Background
    Recent data suggests a trend for prolonged progression-free survival (PFS) in patients with wild-type EGFR (wtEGFR) non-small cell lung cancer (NSCLC) treated with second-line docetaxel over erlotinib. In this same study, however, overall survival (OS) appeared unaffected. In the maintenance setting, erlotinib was also shown to improve both PFS and OS in wtEGFR advanced NSCLC patients. More recently, evaluating serum protein patterns by mass spectroscopy revealed inferior PFS with erlotinib compared to docetaxel in patients with a particular protein pattern. The individual proteins in the mass spectroscopy peaks were not identified. The objective of this study was to develop a multi-analyte serum panel of specific proteins with predictive value for erlotinib versus palliative chemotherapy in pretreated advanced NSCLC patients that were unselected for EGFR mutation status.

    Methods
    74 biomarkers were evaluated using Luminex immunobead assays against a total of 120 patients with stage IV NSCLC that were previously treated with chemotherapy and were unselected for EGFR mutation status. Patients were treated either with single agent erlotinib or platinum-based chemotherapy at the discretion of the treating physician. Patients were evaluated for disease progression using RECIST criteria and association of biomarker with survival outcomes was assessed using Cox proportional hazards regression model. The differential association of the biomarkers in the two treatment groups (erlotinib or chemotherapy) with survival outcomes was assessed using a proportional hazards (PH) interaction model.

    Results
    In univariate PH regression analysis, we identified 7 serum biomarkers (osteopontin, CA-125, sTNF-RII, PlGF, leptin, IGFBP5, and amphiregulin) which were strongly associated (p<0.01) and nine additional biomarkers (IGFBP4, sTNF-RI, CA 15-3, IGFBP1, sIL-2Rα, sFAS, VEGF-A, sIL-1RI, and sIL-4R) which had significant association (p<0.05) with PFS in the erlotinib subgroup (n=92). Similarly, 9 biomarkers (osteopontin, sTNF-RI, sTNF-RII, CA 15-3, sIL-2Rα, epiregulin, PILG, IL6 and CA 125) were found to be strongly associated with OS. In our assessment of differential association with PFS, we found eight serum biomarkers (sIL-2Rα, IL-8, sIL-1RI, Tensascin C, FGF2, HGF, Leptin, and TGF-α) with significant to strongly significant positive interaction terms, thus indicating differentially increased hazard of progression in the chemotherapy subgroup with high biomarker levels. Four markers (IL-8, TGF-α, HGF, VEGF-A) were found to have significantly positive interaction, indicating a decreased hazard of death in the erlotinib group with high biomarker levels; whereas two (sTNF-RII, PSA) had significant negative interaction with OS, demonstrating a increased hazard of death in the erlotinib group.

    Conclusion
    We identified a series of circulating surrogate biomarkers associated with epithelial-to-mesenchymal transition (EMT) that have promise for algorithm development to help physicians determine whether erlotinib as a single agent of chemotherapy is capable of improving outcomes in patients that progressed after first-line platinum-based chemotherapy. Current efforts focus on evaluating biomarker relationships with EGFR mutation status and algorithm validation in an effort to enhance survival in advanced stage NSCLC.