Bevacizumab as first-line treatment for advanced non-small cell lung cancer.

Bevacizumab is a humanized monoclonal antibody (mAb) to vascular endothelial growth factor (VEGF), a major proangiogenic factor in advanced solid tumors. Phase I and II trial results suggested that this agent was well tolerated and could be combined with standard regimens in various solid tumors. An initial randomized phase II trial in advanced non-small cell lung cancer (NSCLC) yielded positive results regarding the potential efficacy of this agent in combination with carboplatin and paclitaxel (CbP). It also identified a safety signal in patients with squamous histology, who appear to have a higher rate of serious and potentially life-threatening pulmonary hemorrhage. Because of this observation, patients with predominantly squamous histology were excluded from the pivotal phase III trials, as were patients with brain metastases and a history of significant hemoptysis. Two phase III trials comparing a standard platinum-based doublet with or without bevacizumab have been reported in advanced NSCLC, both of which met their primary endpoints. The trial reported by the Eastern Cooperative Oncology Group (ECOG 4599) was the first to show an overall survival benefit, as well as a benefit in response rates and progression-free survival resulting from the addition of bevacizumab to CbP. Certain toxicities were increased when bevacizumab was added to CbP, including neutropenia, febrile neutropenia, thrombocytopenia, bleeding (including pulmonary hemorrhage), hypertension and proteinuria. Bevacizumab is the first targeted therapeutic agent to improve survival in advanced NSCLC when added to standard chemotherapeutic regimens.