title: Efficacy and safety of adding an agent to bevacizumab/taxane regimens for the first-line treatment of Her2-negative patients with locally recurrent or metastatic breast cancer: results from seven randomized controlled trials.
abstract: BACKGROUND
  The combined therapy of bevacizumab (BEV) with taxane (paclitaxel or docetaxel) has shown an improvement on progression-free survival (PFS) and objective remission in Her2-negative patients with locally recurrent or metastatic breast cancer (LR/MBC). However, there was no benefit in overall survival (OS). The aim of this study was to evaluate the efficacy and safety of adding an agent to the BEV/taxane regimens for the treatment of Her2-negative patients with LR/MBC in a first-line setting.
  
  
  METHODS
  We searched PubMed, Web of Science, EMBASE, EBSCO, and the Cochrane Library databases for eligible trials. A meta-analysis was performed using Review Manager 5.0 freeware package. We calculated the hazard ratio (HR) for PFS and OS. The odds ratio (OR) was used to calculate objective response rate (ORR) and grade 3/4 drug-related adverse events. The heterogeneity of study outcomes was calculated by the χ (2) test or I (2) statistics.
  
  
  RESULTS
  A total of 1,124 patients from seven randomized controlled trials were analyzed. Our meta-analysis showed that the ORR was significantly improved in the BEV/taxane-based triplet group when compared with the BEV/taxane-based doublet group (OR =1.31, 95% confidence interval [CI]: 1.03-1.67, P=0.03). A subset analysis showed that a similar result was achieved in the triplet group in which a cytotoxic agent was added (OR =1.46, 95% CI: 1.09-1.95, P=0.01). However, the PFS and OS had no statistically significant differences between the two groups (HR =0.87, 95% CI: 0.68-1.13, P=0.31; HR =0.98, 95% CI: 0.82-1.16, P=0.78, respectively). Regarding safety, thromboembolic events, fatigue, and diarrhea (all $grade 3) were more frequently observed in the BEV/taxane-based triplet group (OR =3.8, 95% CI: 1.86-7.79, P=0.0003; OR =1.55, 95% CI: 1.05-2.27, P=0.03; OR =2.1, 95% CI: 1.29-3.41, P=0.003, respectively). Other toxic effects had no statistically significant differences between the two groups.
  
  
  CONCLUSIONS
  Our results showed that adding an agent to BEV/taxane treatment regimens did not significantly improve PFS and prolong OS, except for conferring a significant advantage toward improved ORR in the first-line therapy for Her2-negative patients with LR/MBC. However, its side effects are predictable and manageable.
authors.affiliation: Department of Oncology.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Affiliated Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oncology.
authors.forename: Tiankui
authors.initials: T
authors.lastname: Qiao
authors.affiliation: Department of Oncology.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Oncology.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Yuan
keywords: bevacizumab; breast cancer; docetaxel; meta-analysis; paclitaxel