Antiangiogenic Therapies in Non-Small-Cell Lung Cancer

Abstract

Angiogenesis is frequent in non-small-cell lung cancer (NSCLC) and is associated with more aggressive disease. Many clinical trials have evaluated the addition of antiangiogenic therapy to standard therapies for patients with NSCLC. Bevacizumab, a monoclonal antibody directed against serum vascular endothelial growth factor, in combination with carboplatin–paclitaxel chemotherapy, has been shown to improve survival for patients with NSCLC. However, bevacizumab-based therapy is not suitable for many NSCLC patients, including those with squamous histology, poor performance status, brain metastases, and the presence of bleeding or thrombotic disorders. Similar efficacy has also been seen with carboplatin–pemetrexed followed by maintenance pemetrexed chemotherapy. In the second-line setting, the addition of ramucirumab to docetaxel—or the addition of bevacizumab to paclitaxel—has resulted in a modest improvement in efficacy, although the clinical importance of those findings is questionable. Many trials in NSCLC have also evaluated oral antiangiogenic compounds, both in the first line in combination with chemotherapy and upon disease progression either as combination or single-agent therapy. No clear improvements in overall survival have been observed, although a subgroup analysis of a trial evaluating the addition of nintedanib to docetaxel showed improved survival that was limited to patients with adenocarcinoma. Those findings require validation, however. All of the oral antiangiogenic agents result in added toxicities. Some agents have resulted in an increased risk of death, limiting their development. Available evidence supports a limited number of antiangiogenic therapies for patients with NSCLC, but no biomarkers to help in patient selection are currently available, and additional translational research is needed to identify predictive biomarkers for antiangiogenic therapy.