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Originally published as JCO Early Release 10.1200/JCO.2005.02.477 on March 7 2005

Journal of Clinical Oncology, Vol 23, No 11 (April 10), 2005: pp. 2544-2555
© 2005 American Society of Clinical Oncology.
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Phase I/II Trial Evaluating the Anti-Vascular Endothelial Growth Factor Monoclonal Antibody Bevacizumab in Combination With the HER-1/Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib for Patients With Recurrent Non–Small-Cell Lung Cancer

Roy S. Herbst, David H. Johnson, Eric Mininberg, David P. Carbone, Ted Henderson, Edward S. Kim, George Blumenschein, Jr, Jack J. Lee, Diane D. Liu, Mylene T. Truong, Waun K. Hong, Hai Tran, Anne Tsao, Dong Xie, David A. Ramies, Robert Mass, Somasekar Seshagiri, David A. Eberhard, Sean K. Kelley, Alan Sandler

From the Departments of Thoracic/Head & Neck Medical Oncology, Biostatistics, and Diagnostic Radiology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX; Departments of Medicine and Hematology/Oncology, Vanderbilt University Medical School, The Vanderbilt-Ingram Cancer Center, Nashville, TN; Departments of Pharmacokinetic and Pharmacodynamic Sciences, BioOncology, Microbiology and Pathology, Genentech Inc, South San Francisco, CA

Address reprint requests to Alan Sandler, MD, Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN 37232-6307; e-mail: alan.sandler{at}vanderbilt.edu.

PURPOSE: Bevacizumab (Avastin; Genentech, South San Francisco, CA) is a recombinant, humanized anti-vascular endothelial growth factor monoclonal antibody. Erlotinib HCl (Tarceva, OSI-774; OSI Pharmaceuticals, New York, NY) is a potent, reversible, highly selective and orally available HER-1/epidermal growth factor receptor tyrosine kinase inhibitor. Preclinical data in various xenograft models produced greater growth inhibition than with either agent alone. Additionally, both agents have demonstrated benefit in patients with previously treated non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: A phase I/II study in two centers examined erlotinib and bevacizumab (A+T) in patients with nonsquamous stage IIIB/IV NSCLC with ≥ one prior chemotherapy. In phase I, erlotinib 150 mg/day orally plus bevacizumab 15 mg/kg intravenously every 21 days was established as the phase II dose, although no dose-limiting toxicities were observed. Phase II assessed the efficacy and tolerability of A+T at this dose. Pharmacokinetic parameters were evaluated.

RESULTS: Forty patients were enrolled and treated in this study (34 patients at phase II dose); the median age was 59 years (range, 36 to 72 years), 21 were female, 30 had adenocarcinoma histology, nine were never-smokers, and 22 had ≥ two prior regimens (three patients had ≥ four prior regimens). The most common adverse events were mild to moderate rash, diarrhea, and proteinuria. Preliminary data showed no pharmacokinetic interaction between A+T. Eight patients (20.0%; 95% CI, 7.6% to 32.4%) had partial responses and 26 (65.0%; 95% CI, 50.2% to 79.8%) had stable disease as their best response. The median overall survival for the 34 patients treated at the phase II dose was 12.6 months, with progression-free survival of 6.2 months.

CONCLUSION: Encouraging antitumor activity and safety of A+T support further development of this combination for patients with advanced NSCLC and other solid tumors.

Supported by Genentech Inc, South San Francisco, CA

Previously presented at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, May 31-June 3; 40th ASCO Annual Meeting, New Orleans, LA, June 5-8, 2004; and 10th World Congress on Lung Cancer, Vancouver, Canada, August 10-14, 2004.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.




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