Bevacizumab: a review of its use in combination with paclitaxel or capecitabine as first-line therapy for HER2-negative metastatic breast cancer

Abstract

Bevacizumab (Avastin™) is a humanized monoclonal antibody directed against vascular endothelial growth factor. In patients with human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer, bevacizumab is indicated as first-line therapy in combination with paclitaxel, or in combination with capecitabine when treatment with other chemotherapy options, including taxanes or anthracyclines, is not considered appropriate. This article reviews the efficacy and tolerability of these combination therapies in the first-line treatment of patients with metastatic breast cancer, and summarizes the pharmacological properties of bevacizumab. In randomized, controlled, phase III trials in patients with predominantly HER2-negative metastatic or locally recurrent breast cancer, the addition of bevacizumab to paclitaxel or capecitabine significantly prolonged progression-free survival (PFS; investigator assessment) by a median of 5.9 and 2.9 months, respectively, relative to paclitaxel or capecitabine alone. It also significantly increased the objective response rate, but not overall survival. Independent reviews of data supported the results of the primary analyses of investigator-assessed PFS. However, as the efficacy of bevacizumab in combination with capecitabine appears to be less than that of other available options, it should be used only if treatment with other chemotherapy options are not considered appropriate. The addition of bevacizumab to paclitaxel had no significant adverse effects on health-related quality of life. Efficacy data from two routine clinical practice studies were generally consistent with those from the phase III trials. Bevacizumab had generally acceptable tolerability when administered in combination with paclitaxel or capecitabine as first-line therapy in these studies, and adverse events were consistent with the known tolerability profiles of the individual agents. The most common adverse events associated with bevacizumab combination therapy in phase III trials were sensory neuropathy and grade ≥3 hypertension, occurring more frequently with combination therapy than with chemotherapy alone. Potentially life-threatening events, such as venous thromboembolism, gastrointestinal perforation, arterial thromboembolism, haemorrhage and left ventricular dysfunction, occurred in ≤5% of patients receiving combination therapy in these trials. In conclusion, bevacizumab administered in combination with paclitaxel, or in combination with capecitabine if other chemotherapy regimens are not appropriate, may be considered as an option for the first-line treatment of patients with HER2-negative metastatic breast cancer.