Originally published as JCO Early Release 10.1200/JCO.2007.12.3026 on October 1 2007

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Phase II Study of Efficacy and Safety of Bevacizumab in Combination With Chemotherapy or Erlotinib Compared With Chemotherapy Alone for Treatment of Recurrent or Refractory Non–Small-Cell Lung Cancer

Roy S. Herbst, Vincent J. O'Neill, Louis Fehrenbacher, Chandra P. Belani, Philip D. Bonomi, Lowell Hart, Ostap Melnyk, David Ramies, Ming Lin, Alan Sandler

From The M.D. Anderson Cancer Center, Houston, TX; Genentech Inc, South San Francisco; Kaiser Permanente Northern California, Vallejo; Bay Area Cancer Research Group, Concord, CA; University of Pittsburgh Cancer Institute, Pittsburgh, PA; Rush University Medical Center, Chicago, IL; Florida Cancer Specialists, Ft Meyers, FL; and Vanderbilt University, Nashville, TN

Address reprint requests to Roy S. Herbst, MD, PhD, The M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX 77030; e-mail: rherbst{at}mdanderson.org

Purpose Bevacizumab, a humanized anti–vascular endothelial growth factor monoclonal antibody, and erlotinib, a reversible, orally available epidermal growth factor receptor tyrosine kinase inhibitor, have demonstrated evidence of a survival benefit in the treatment of non–small-cell lung cancer (NSCLC). A single-arm phase I and II study of bevacizumab plus erlotinib demonstrated encouraging efficacy, with a favorable safety profile.

Patients and Methods A multicenter, randomized phase II trial evaluated the safety of combining bevacizumab with either chemotherapy (docetaxel or pemetrexed) or erlotinib and preliminarily assessed these combinations versus chemotherapy alone, as measured by progression-free survival (PFS). All patients had histologically confirmed nonsquamous NSCLC that had progressed during or after one platinum-based regimen.

Results One hundred twenty patients were randomly assigned and treated. No unexpected adverse events were noted. Fewer patients (13%) in the bevacizumab-erlotinib arm discontinued treatment as a result of adverse events than in the chemotherapy alone (24%) or bevacizumab-chemotherapy (28%) arms. The incidence of grade 5 hemorrhage in patients receiving bevacizumab was 5.1%. Although not statistically significant, relative to chemotherapy alone, the risk of disease progression or death was 0.66 (95% CI, 0.38 to 1.16) among patients treated with bevacizumab-chemotherapy and 0.72 (95% CI, 0.42 to 1.23) among patients treated with bevacizumab-erlotinib. One-year survival rate was 57.4% for bevacizumab-erlotinib and 53.8% for bevacizumab-chemotherapy compared with 33.1% for chemotherapy alone.

Conclusion Results for PFS and overall survival favor combination of bevacizumab with either chemotherapy or erlotinib over chemotherapy alone in the second-line setting. No unexpected safety signals were noted. The rate of fatal pulmonary hemorrhage was consistent with previous bevacizumab trials. The toxicity profile of the bevacizumab-erlotinib combination is favorable compared with either chemotherapy-containing group.

published online ahead of print at www.jco.org on October 1, 2007.

Supported by Genentech Inc, South San Francisco, CA.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA; the 18th Annual European Organisation for Research and Treatment of Cancer–National Cancer Institute–American Association for Cancer Research Symposium on Molecular Targets and Cancer Therapeutics, November 7-10, 2006, Prague, Czech Republic; and the 4th Annual International Association for the Study of Lung Cancer International Chicago Symposium on Malignancies of the Chest and Head and Neck, October 26-28, 2006, Chicago, IL.

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

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