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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

  • 12483

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    P3.06-043 - Modulation of the cyclooxygenase pathway is associated with efficacy in a randomized phase II trial of erlotinib and celecoxib or placebo in advanced non-small cell lung cancer (NSCLC) (ID 2899)

    09:30 - 09:30  |  Author(s): H. Wang
    • Abstract

    Background
    Combined epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and cyclooxygenase-2 (COX-2) inhibition has been shown to potentiate responses in NSCLC, and may overcome resistance in wild type EGFR tumors. Several biomarkers have been used to evaluate effective targeting of the COX-2 pathway. COX-2 expression by immunohistochemistry (IHC) and urinary 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (uPGEM) have identified patients who may derive benefit from COX-2 inhibition. We evaluated these markers in association with PFS and tumor response in our randomized, placebo controlled trial of erlotinib and high dose celecoxib in advanced NSCLC patients.

    Methods
    Pts with stage IIIB/IV NSCLC who progressed following at least one line of therapy or refused standard chemotherapy were randomized to erlotinib (150mg/day)/high dose celecoxib (600mg/2x day) v E/P. Urinary prostaglandin E2-metabolite (uPGEM) was assessed at baseline, week 4 and week 8 of therapy. Immunohistochemical evaluation of COX-2 was performed on archival tissue.

    Results
    87 pts had urine assessed and 38 pts had additional evaluable tissue following EGFR mutation analysis. PFS was significantly improved in patients with wild type EGFR tumors (3.2 v 1.8 months, HR = 0.54, p = 0.03). Previously established normal uPGEM levels for men and women were used to determine high and low baseline values. 59 pts (67%) had high and 29 pts (33%) had low uPGEM at baseline. Elevated baseline uPGEM was associated with improved PFS for patients who received high dose celecoxib (5.6 v 2.2 months, p = 0.09). Pts with low baseline uPGEM did not benefit from celecoxib. Further assessment of COX-2 and E-cadherin was performed by IHC and correlations will be presented.

    Conclusion
    UPGEM is an easily assessed biomarker that is associated with improved outcomes in patients treated with high dose celecoxib and erlotinib with advanced NSCLC. Tumor levels of COX-2 and E-cadherin may refine our ability to best define a population who will benefit from COX-2 and EGFR targeted therapy in future studies. Supported by NIH 1P50 CA90388, K12 CA01727, Phase One Foundation and medical research funds from the Dept of Veterans’ Affairs.