Targeting Angiogenesis in Non-Small Cell Lung Cancer (NSCLC)

The management of NSCLC has undergone a paradigm shift in the last 5 years with the survival advantage demonstrated by the addition of bevacizumab to standard frontline platinum-based doublet specifically, paclitaxel and carboplatin. The increased toxicity observed in patients with squamous histology and in elderly patients treated with angiogenesis-targeting agents has led to even greater scrutiny of other subpopulations of patients. Although recently, several antiangiogenetic agents have been developed and tested in clinical trials, bevacizumab remains the only vasculartargeted agents to show overall survival benefit when combined with a cytotoxic agent in the frontline setting. The realization of the potential promise of personalized medicine requires that the appropriate treatment be given to the most appropriate group of patients. Given the modest benefit and the significant toxicity associated with the use of antiangiogenesis agents in NSCLC patients, it is highly desirable that predictive markers of response and or toxicity be established to assist in the optimal selection of patients. Although a number of plasma-, tissueand genomic-based markers have been explored, none of these has been robust or sensitive enough to reproducibly discriminate responding from non-responding patients. The presence of squamous differentiation on histologic evaluation remains the only established marker that predicts for increased risk of hemorrhagic complications. In this review, we discuss data establishing the role of angiogenesis-targeting agents and the clinical value of putative markers of angiogenesis.