Bevacizumab combined with two-weekly paclitaxel as first-line therapy for metastatic breast cancer.

Background: Metastatic breast cancer remains a major clinical issue despite progress achieved in recent years. Three randomised trials have demonstrated the benefit of combining bevacizumab with various taxane schedules. Herein, this study sought to investigate an alternative bevacizumab-taxane regimen as first-line treatment for metastatic breast cancer. Patients and Methods: Patients with metastatic breast cancer and who received first-line bevacizumab 10 mg/kg with paclitaxel 135 mg/m 2 every 2 weeks were studied. Results: All 43 enrolled patients were evaluable for efficacy and safety. The response rate was 58%; a further 40% achieved stable disease. After a median follow-up of 16 months, disease had progressed in 9 patients (21%). Treatment was well tolerated: grade 4 toxicities were absent; grade 3 adverse events comprised neutropenia (5%; no febrile neutropenia), hypertension (2%) and neuropathy (2%). Conclusion: This regimen may provide improved patient acceptability, quality of life and pharmacoeconomic benefits over a weekly paclitaxel schedule, and deserves further evaluation. The crucial role of angiogenesis in tumour growth is firmly established and angiogenic pathways are important targets in treating many solid tumours, including breast cancer (BC). In metastatic BC, the only available anti-angiogenic agent is bevacizumab, which directly inhibits all isoforms of vascular endothelial growth factor. Three randomised, phase III trials (E2100, AVADO, RIBBON-1) in the first-line setting have demonstrated the efficacy and tolerability of combining bevacizumab with taxane-based therapy, showing significantly improved progression-free survival (PFS, the primary endpoint) and response rate compared with chemotherapy alone (1-3). Furthermore, the RIBBON-1 trial showed that the effect of combining bevacizumab with taxanes appears to apply more generally to standard first-line chemotherapy regimens, including anthracycline-based combinations and capecitabine. While these trials provide evidence of the efficacy and tolerability of combining bevacizumab with weekly paclitaxel, 3-weekly docetaxel and 3-weekly nab-paclitaxel, this study aimed to determine the effect of combining bevacizumab with a 2-weekly schedule of paclitaxel. Similar dose-dense regimens have been evaluated in metastatic BC in combination with chemotherapy agents (4-8). A 2-weekly regimen is often used in the host clinic with the aim of improving patient convenience compared with weekly paclitaxel, while maintaining dose intensity. Previously published data demonstrated the efficacy of bevacizumab combined with 2-weekly paclitaxel in pretreated metastatic BC (9). Herein, the efficacy of this regimen in the first-line setting was assessed, including a bevacizumab maintenance phase to evaluate continuation of bevacizumab after completion of a fixed duration of chemotherapy.