Phase II, randomized, biomarker identification trial (MARK) for erlotinib in patients with advanced pancreatic carcinoma

David Propper, I. Davidenko, J. Bridgewater, L. Kupcinskas, A. Fittipaldo, C. Hillenbach, B. Klughammer, M. Ducreux

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    27 Citations (Scopus)

    Résumé

    Background: A prospective, randomized phase II study, with mandatory tumor sampling at current disease stage, aimed to identify biomarkers predictive of improved progression-free survival (PFS) in patients with pancreatic cancer treated with erlotinib. Patients and methods: Patients with histologically/cytologically confirmed, unresectable, locally advanced/metastatic pancreatic cancer, who had failed on or were unsuitable for first-line chemotherapy, underwent a tumor biopsy and were then randomized to receive once-daily erlotinib 150 mg or placebo. The primary end point was identification of biomarkers predicting improved PFS with erlotinib. Secondary end points included PFS, overall survival, response and toxicity. Results: At data cut-off, 207 patients were enrolled and analyzed. Prespecified biomarker analyses of EGFR protein expression, EGFR gene copy number/mutations/polymorphisms and KRAS mutations did not identify any subgroups with a detrimental effect or a strong benefit for PFS with erlotinib. In the primary analysis, the median PFS was 6.1 versus 5.9 weeks in the erlotinib and placebo arms, respectively [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.63-1.10; P = 0.1909]. However, observed baseline imbalances indicated worse prognosis in the erlotinib arm. After adjustment for baseline characteristics, a significant PFS benefit for erlotinib was observed (HR 0.68; 95% CI 0.50-0.91; P = 0.0102). Exploratory biomarker analyses showed patients with high baseline serum amphiregulin levels might benefit from erlotinib. Conclusion: This study in patients with inoperable pancreatic cancer did not identify any prespecified biomarkers predictive of PFS benefit with erlotinib. Exploratory analyses suggested high amphiregulin might predict PFS benefit from erlotinib.

    langue originaleAnglais
    Pages (de - à)1384-1390
    Nombre de pages7
    journalAnnals of Oncology
    Volume25
    Numéro de publication7
    Les DOIs
    étatPublié - 1 janv. 2014

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