Work

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

Year: 2013

Type: article

Abstract: // Gerald S. Falchook 1 , Aung Naing 1 , David S. Hong 1 , Ralph Zinner 1 , Siqing Fu 1 , Sarina A. Piha-Paul 1 , Apostolia M. Tsimberidou 1 , Sonia K. Morgan-Linnell 1 , Yunfang Jiang 1 , Christel Bastida 1 , Jennifer J. Wheler 1 , and Razelle Kurzrock 2 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 Correspondence: Gerald Falchook, email: // Keywords : Erlotinib, Cetuximab, Bevacizumab, EGFR, VEGF Received : December 06, 2012, Accepted : January 12, 2013, Published : January 14, 2013 Abstract 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.763