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Lung Cancer

Bevacizumab and Erlotinib: A Promising New Approach to the Treatment of Advanced NSCLC

^aThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA; ^bVanderbilt University Medical Center, Nashville, Tennessee, USA

Key Words. NSCLC • EGFR • VEGF • Erlotinib • Bevacizumab

Correspondence: Roy Herbst, M.D., Ph.D., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. Telephone: 713-792-6363; Fax: 713-792-1220; e-mail: rherbst{at}mdanderson.org

Received May 5, 2008; accepted for publication September 29, 2008; first published online in THE ONCOLOGIST Express on November 8, 2008.

Disclosure: Employment/leadership position: None; Intellectual property rights/inventor/patent holder: None; Consultant/advisory role: Roy S. Herbst, Genentech, AstraZeneca, Amgen, ImClone; Alan Sandler, ImClone; Honoraria: Alan Sandler, Genentech, OSI; Research funding/contracted research: Roy S. Herbst, Genentech, AstraZeneca, Amgen; Alan Sandler, Genentech, OSI; Ownership interest: None; Expert testimony: None; Other: None.

The authors disclose that the article discusses unlabeled, investigational, or alternate uses of erlotinib, bevacizumab, cetuximab, and vandetanib for NSCLC.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

Biologic agents that target molecules involved in tumor growth, progression, and pathological angiogenesis—such as the human epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF)—have demonstrated efficacy in patients with non-small cell lung cancer (NSCLC). Erlotinib (Tarceva®; OSI Pharmaceuticals, Inc., Melville, NY, Genentech, Inc., South San Francisco, CA, and F. Hoffmann-La Roche Ltd, Basel, Switzerland), a highly selective tyrosine kinase inhibitor that inhibits EGFR, and bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA, and F. Hoffmann-La Roche Ltd, Basel, Switzerland), a VEGF-targeted recombinant humanized monoclonal antibody, have displayed very encouraging activity in a randomized phase II trial in patients with previously treated NSCLC. Because erlotinib and bevacizumab act on two different pathways critical to tumor growth and dissemination, administering these drugs concomitantly may confer additional clinical benefits to cancer patients with advanced disease, by virtue of their complementary (or additive) antitumor activity. The combination of bevacizumab plus erlotinib may prove to be a viable second-line alternative to chemotherapy or erlotinib monotherapy in patients with NSCLC. The benefits of the combination may be further enhanced by selecting for patients who are likely to respond to this therapy. While a number of potential predictive markers have been identified for erlotinib, their value remains to be confirmed in prospective trials. In addition, the application of such personalized therapy will also depend on the availability of validated screening methods.