Dual EGFR inhibition in combination with anti-VEGF treatment: A phase I clinical trial in non-small cell lung cancer

Gerald S. Falchook, Aung Naing, David S. Hong, Ralph Zinner, Siqing Fu, Sarina A. Piha-Paul, Apostolia M. Tsimberidou, Sonia K. Morgan-Linnell, Yunfang Jiang, Christel Bastida, Jennifer J. Wheler, Razelle Kurzrock

    Research output: Contribution to journalArticlepeer-review

    31 Scopus citations

    Abstract

    Background: Preclinical data indicate EGFR signals through both kinasedependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models. Methods: We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with non-small cell lung cancer (NSCLC) was analyzed for safety and response. Results: Thirty-four patients with NSCLC (median four prior therapies) received treatment on a range of dose levels. The most common treatment-related grade =2 adverse events were rash (n=14, 41%), hypomagnesemia (n=9, 27%), and fatigue (n=5, 15%). Seven patients (21%) achieved stable disease (SD)≥6 months, two achieved a partial response (PR) (6%), and two achieved an unconfirmed partial response (uPR) (6%) (total=32%). We observed SD≥6 months/PR/uPR in patients who had received prior erlotinib and/or bevacizumab, those with brain metastases, smokers, and patients treated at lower dose levels. Five of 16 patients (31%) with wild-type EGFR experienced SD≥6 months or uPR. Correlation between grade of rash and rate of SD≥6 months/PR was observed (p<0.01). Conclusion: The combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC.

    Original languageEnglish (US)
    Pages (from-to)118-127
    Number of pages10
    JournalOncotarget
    Volume4
    Issue number1
    DOIs
    StatePublished - 2013

    Keywords

    • Bevacizumab
    • Cetuximab
    • EGFR
    • Erlotinib
    • VEGF

    ASJC Scopus subject areas

    • Oncology

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