Emerging safety data for bevacizumab in advanced non-small-cell lung cancer.

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor, confers improved clinical outcomes in a range of tumor types when administered in combination with chemotherapy. In a pivotal phase III trial (E4599), bevacizumab became the first agent to extend overall survival beyond 1 year when combined with first-line chemotherapy for advanced, metastatic, or recurrent non-squamous non-small-cell lung cancer (NSCLC). In a recent phase III trial (AVAiL; Avastin in Lung Cancer), which investigated the safety and efficacy of 2 bevacizumab doses in combination with cisplatin/gemcitabine, bevacizumab-based therapy significantly delayed disease progression in patients with advanced, metastatic, or recurrent non-squamous NSCLC. Based on these positive data, bevacizumab in combination with chemotherapy has received US and European Union approval for the first-line treatment of unresectable advanced, metastatic, or recurrent predominantly non-squamous NSCLC. Bevacizumab-based therapy has a well-characterized safety profile. Clinically relevant bevacizumab-associated adverse events reported in clinical trials to date include bleeding, hypertension, proteinuria, thrombotic events, wound-healing complications, and gastrointestinal perforations. Emerging safety data for bevacizumab in NSCLC from the recent AVAiL trial indicate that, as in clinical trials in other indications, adverse events were generally manageable using standard clinical techniques and rarely required discontinuation of bevacizumab therapy. In the AVAiL trial, grade ≥ 3 hypertension, bleeding, and proteinuria rates were modestly higher in the bevacizumab arms than in the placebo arm, although the overall incidence of grade ≥ 3 adverse events was similar in the placebo and bevacizumab arms. Recommendations for the monitoring and management of bevacizumab-associated adverse events are discussed.