Safety of bevacizumab in patients with metastatic breast cancer.

Five randomized phase III trials - AVF2119g, E2100, AVADO, RIBBON-1, and RIBBON-2 - have reported data on the efficacy and safety of bevacizumab, combined with a variety of chemotherapy agents and in various settings, in patients with metastatic breast cancer (MBC). The E2100 trial demonstrated a significant improvement in progression-free survival according to the independent review facility, from 5.8 to 11.3 months when bevacizumab was combined with paclitaxel (p < 0.0001) as first-line therapy in patients with HER2-nonamplified MBC; subsequent trials of bevacizumab as first-line (AVADO, RIBBON-1) and second-line (RIBBON-2) therapy for patients with HER2-nonamplified MBC have also met their primary end point of prolonging progression-free survival (PFS). Accumulating safety data for bevacizumab in MBC show that it is generally well tolerated and associated with predictable adverse events, including hypertension and proteinuria. The majority of adverse events are mild and manageable, but bevacizumab is also associated with some severe toxicities. The management of bevacizumab-related adverse events in MBC has improved with increased experience. This review summarizes bevacizumab efficacy in MBC and focuses on bevacizumab-related toxicities as reported in 5 phase III clinical trials. Current adverse event management strategies, based on guidelines and experience from these trials, are outlined.