Chemotherapy plus bevacizumab in the first-line tratment of non-small cell lung cancer: benefits, risks and limitations

Though chemotherapy remains a mainstay of non-small cell lung cancer (NSCLC) treatment, its efficacy has probably reached a plateau. The management of advanced NSCLC has evolved considerably in recent years due to a progressive understanding of tumour biology and the identification of promising molecular targets. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF), a key signalling protein in tumour neoangiogenesis, growth and dissemination. The finding in study E4599 of a survival benefit for carboplatin-paclitaxel plus bevacizumab over chemotherapy alone led the U.S. FDA to approve the novel combination for the first-line treatment of patients with advanced, non-squamous NSCLC. This study is the first to show a survival advantage with the addition of a targeted agent to chemotherapy in this setting: in particular, for the first time the survival of NSCLC patients has been extended beyond one year. Recently, in a randomised phase III trial, patients receiving cisplatin-gemcitabine plus bevacizumab experienced a significantly longer progression-free survival compared to the standard arm. Based on these data, the EMEA has just issued a positive opinion to extend the drug's indication to include first-line treatment - in combination with any platinum-based chemotherapy - of advanced, non-squamous NSCLC. The aim of this review is to provide an overview of the evidence supporting the emergence of this new treatment. Key questions - including the optimal dose of bevacizumab, safety of the drug in special populations, the selection of patients most likely to benefit from the treatment, the role of maintenance - are addressed.