Dual EGFR inhibition in combination with anti-VEGF treatment: A phase I clinical trial in non-small cell lung cancer
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Gerald S. Falchook1, Aung Naing1, David S. Hong1, Ralph Zinner1, Siqing Fu1, Sarina A. Piha-Paul1, Apostolia M. Tsimberidou1, Sonia K. Morgan-Linnell1, Yunfang Jiang1, Christel Bastida1, Jennifer J. Wheler1, and Razelle Kurzrock2
1 Department of Investigational Cancer Therapeutics (Phase I Program), U.T. MD Anderson Cancer Center, Houston, TX
2 Moores Cancer Center at the University of California, San Diego
Gerald Falchook, email:
Keywords: Erlotinib, Cetuximab, Bevacizumab, EGFR, VEGF
Received: December 06, 2012, Accepted: January 12, 2013, Published: January 14, 2013
BACKGROUND: Preclinical data indicate EGFR signals through both kinase-dependent 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.
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