Antiangiogenic Agents for the Treatment of Nonsmall Cell Lung Cancer: Characterizing the Molecular Basis for Serious Adverse Events

Abstract

Novel agents to reduce angiogenesis by targeting vascular endothelial growth factor and other proangiogenic signaling pathways are being developed for advanced nonsmall cell lung cancer. Antibody-based therapies (e.g., aflibercept) and multitargeted tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, and BIBF 1120) are being evaluated in phase III clinical trials. Some antiangiogenic agents have demonstrated distinct profiles in producing a variety of nonhematologic toxicities, including bleeding/hemorrhage, venous and arterial thromboembolic events, gastrointestinal perforation, hypertension, and proteinuria. Elucidating the molecular basis of these toxicities may lead to clinical benefits by improving patient selection and allowing for the development of effective prevention and management strategies.

Keywords: :

• Angiogenesis
• Biologic therapy
• Lung cancer

ACKNOWLEDGMENTS

This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). Copyediting, editorial, and production assistance were provided by Alyssa Tippens, PhD, of MedErgy, which was contracted by BIPI for these services. The authors meet the ICMJE criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), were involved at all stages of manuscript development, and fully accept responsibility for all content and editorial decisions. The authors received no compensation related to the development of the manuscript.