Anti-angiogenesis in Personalized Therapy of Lung Cancer
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Upregulation of angiogenesis is a frequent occurrence in lung cancer and is reported to represent a negative prognostic factor. This provides a rationale for the development and evaluation of anti-angiogenic agents. To date bevacizumab, a monoclonal antibody directed against serum VEGF, is the only anti-angiogenic agent that has demonstrated improved overall survival for patients with lung cancer. Meta-analysis of trials of bevacizumab in combination with platinum-based chemotherapy for NSCLC, show a 10% reduction in the risk of death (HR 0.90, 95% CI 0.81-0.99). However, therapy with bevacizumab is limited to NSCLC patients with non-squamous histology, good performance status, no brain metastases and the absence of bleeding or thrombotic disorders. More recently, similar survival was observed in a non bevacizumab containing regimen of carboplatin, pemetrexed and maintenance pemetrexed. Multiple oral anti-angiogenic compounds have been evaluated in NSCLC, both in first-line therapy, or upon disease progression. The majority of agents have shown some evidence of activity, but none have clearly demonstrated improvements in overall survival. Increased toxicities have been observed, including an increased risk of death for some agents, limiting their development. Promising data exist for sunitinib in patients with heavily pre-treated NSCLC, and nintedanib in combination with docetaxel, as second-line therapy for NSCLC. However, these findings require validation. Currently, there is no established role for anti-angiogenic therapy in SCLC, although there is some promise for sunitinib as maintenance therapy following platinum and etoposide chemotherapy. The challenge for anti-angiogenic therapy is to understand whether treatment effects in a subpopulation, are lost among a larger unselected population of patients. There is a need for additional translational research to identify predictive biomarkers for anti-angiogenic therapy.