Spotlight on bevacizumab in metastatic colorectal cancer

Bevacizumab (Avastin (R)) is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that is used to inhibit VEGF function in vascular endothelial cells and thereby inhibit tumor angiogenesis, upon which solid tumors depend for growth and metastasis. The addition of bevacizumab to fluoropyrimidine-based chemotherapy, with or without irinotecan or oxaliplatin, in both the first- and second-line treatment of metastatic colorectal cancer, significantly increased median progression-free survival or time to disease progression in most randomized controlled trials. Bevacizumab was generally, but not always, associated with a survival advantage; in phase III trials, the increases in median overall survival attributable to bevacizumab were 4.7 months with first-line therapy and 2.1 months with second-line therapy. In some studies, patients experienced clinical improvement without an apparent overall survival benefit. Bevacizumab had acceptable tolerability, with the majority of adverse events being generally mild and clinically manageable. However, from the UK National Health Service perspective, bevacizumab was not considered to be cost effective in combination with bolus fluorouracil/leucovorin (folinic acid) or irinotecan/bolus fluorouracil/leucovorin. Additional pharmacoeconomic analyses from different perspectives and using clinical data for combinations with the more efficacious infusional fluorouracil/leucovorin plus oxaliplatin or irinotecan chemotherapy regimens are required. Although cost effectiveness may be a concern, the combination of bevacizumab and fluoropyrimidine-based chemotherapy has potential in the treatment of metastatic colorectal cancer.