New options for integrating antiangiogenic therapy and platinum-based first-line chemotherapy for advanced...

The essential role of angiogenesis in tumor growth and metastasis is well established. The key mediator of angiogenesis, vascular endothelial growth factor (VEGF), is a rational target for novel therapy. High VEGF levels correlate positively with reduced overall survival (OS) and relapse-free survival. Several molecular targeted agents that inhibit VEGF or its receptors are currently in late-stage development or available for the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Bevacizumab is a humanized monoclonal antibody against VEGF that has proven efficacy when combined with different chemotherapy regimens. In the pivotal US phase III trial (E4599) combining bevacizumab with carboplatin/paclitaxel, significantly improved clinical outcomes were observed in terms of OS, progression-free survival (PFS), and response rate (RRs). Although the phase III AVAiL (Avastin in Lung Cancer) trial (BO17704) combining bevacizumab with cisplatin/gemcitabine also showed improved outcomes in terms of PFS and RR, OS data is immature. Bevacizumab is the first agent to improve clinical outcomes when combined with doublet chemotherapy and administered until disease progression. Herein, key clinical data from trials of antiangiogenic agents in the first-line treatment of NSCLC are discussed, with a focus on bevacizumab, currently the only approved antiangiogenic agent for the treatment of NSCLC. The optimal integration of these agents into current and future first-line treatment regimens will be discussed, stressing the importance of therapeutic administration until disease progression. The promising activity of antiangiogenic agents in the advanced disease setting, allied with growing understanding of their novel modes of action, holds therapeutic promise for their future application in early-stage disease.