Bevacizumab in non small cell lung cancer: Development, current status and issues

Bevacizumab is a monoclonal antibody directed against Vascular Endothelial Growth Factor (VEGF). Evidence about its efficacy in addition to first-line chemotherapy in non-small-cell-lung-cancer (NSCLC) has been produced by two large randomized phase III clinical trials (ECOG 4599 and AVAiL), conducted in a clinically selected population with non-squamous histology and without major risk factors for bleeding. In the ECOG 4599 trial, the addition of bevacizumab (15 mg/kg) to carboplatin plus paclitaxel produced a statistically significant and clinically relevant improvement in overall survival (OS), that was the primary endpoint of the trial (12.3 months vs 10.3 months, HR 0.79; p=0.003). Furthermore, patients receiving bevacizumab showed a significant improvement in progression-free survival (PFS) and in objective response rates. Treatment with bevacizumab was well tolerated by the majority of patients, but was still associated with increased risk of clinically significant bleeding (4.4% vs 0.7%, p