Tumor Biology

, Volume 36, Issue 3, pp 1933–1941 | Cite as

The efficacy and safety of bevacizumab combined with chemotherapy in treatment of HER2-negative metastatic breast cancer: a meta-analysis based on published phase III trials

  • Yuan Fang
  • Xinlan Qu
  • Boran Cheng
  • Yuanyuan Chen
  • Zhenmeng Wang
  • Fangfang Chen
  • Bin Xiong
Research Article


Bevacizumab (Bev) combined with chemotherapy significantly improves progression-free survival (PFS) but not overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The efficacy and safety depend on the type of chemotherapy combined with Bev. We performed a meta-analysis of phase III trials to evaluate the efficacy and safety of Bev + standard chemotherapy for HER2-negative MBC. The Cochrane Central Register of Controlled Trials, the Cochrane databases, EMBASE, MEDLINE, and were analyzed. The primary outcomes included PFS, OS, and toxicity. Event-based hazard ratios (HRs) and relative risks (RRs) were expressed with the 95 % confidence intervals (CIs). Four randomized controlled trials consisting of 3082 patients were included. Bev + standard chemotherapy improved PFS (HR 0.70, CI 0.64–0.77, P = 0.000) but had no effect on OS (HR 0.92, CI 0.82–1.02, P = 0.119). Bev + chemotherapy increased the incidence of febrile neutropenia (RR 1.45, CI 1.00 to 2.09, P = 0.048), proteinuria (RR 11.68, CI 3.72–36.70, P = 0.000), sensory neuropathy (RR 1.33, CI 1.05–1.70, P = 0.020), and grade ≥3 hypertension (RR 13.94, CI 7.06–27.55, P = 0.000). No differences in efficacy were observed between Bev + paclitaxel and Bev + capecitabine (Cape), but Bev + Cape increased the incidence of neutropenia. Bev + standard chemotherapy improved PFS in HER2-negative MBC patients. No benefit in OS was observed. Bev + Cape and Bev + paclitaxel had similar treatment efficacy, but Bev + Cape had a higher incidence of neutropenia.


Bevacizumab Chemotherapy HER2-negative Metastatic breast cancer Meta-analysis 



This work was supported by the National High Technology Research and Development Program of China (Grant Nos. 2012AA02A502 and 2012AA02A506). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author contributions

Conceived and designed the experiments: YF, XL-Q, and BX. Analyzed the data: YF, XL-Q, YY-C, and FF-C. Performed the selection of data: YF, BR-C, and ZM-W. Wrote the paper: YF and XL-Q.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yuan Fang
    • 1
  • Xinlan Qu
    • 2
  • Boran Cheng
    • 1
  • Yuanyuan Chen
    • 1
  • Zhenmeng Wang
    • 1
  • Fangfang Chen
    • 1
  • Bin Xiong
    • 1
  1. 1.Department of OncologyZhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study CenterWuhanPeople’s Republic of China
  2. 2.Department of Obstetrics and GynecologyZhongnan Hospital of Wuhan UniversityWuhanPeople’s Republic of China

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