Utility of Hypertension as a Surrogate Marker for Efficacy of Antiangiogenic Therapy in NSCLC

Abstract

A plateau has been reached in the efficacy of cytotoxic chemotherapy for non-small cell lung cancer (NSCLC), highlighting the need for novel treatments for this poor-prognosis malignancy. Antiangiogenic agents, including the approved vascular endothelial growth factor (VEGF)-targeted monoclonal antibody, bevacizumab, as well as a number of investigational tyrosine kinase inhibitors (TKIs) that simultaneously target multiple angiogenic pathways, have demonstrated activity in patients with NSCLC. However, unlike the epidermal growth factor receptor (EGFR) TKIs erlotinib and gefitinib, for which the presence of EGFR-activating mutations are now known to predict response, no validated markers currently exist for the efficacy of antiangiogenic agents. Hypertension has been associated with antiangiogenic therapy and has also been evaluated as a surrogate marker for efficacy with this class of agents, although analyses, to date, have yielded conflicting results. This review provides a summary of currently available, clinically relevant data on the incidence of hypertension with VEGF-targeted antibodies and multitargeted antiangiogenic TKIs in advanced NSCLC and discusses the potential predictive role of hypertension on antiangiogenic therapy in such patients.