title: Efficacy and Safety Profile of Combining Sorafenib with Chemotherapy in Patients with HER2-Negative Advanced Breast Cancer: A Meta-analysis.
abstract: OBJECTIVE
  The aim of the study was to evaluate the efficacy and safety of combining sorafenib with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.
  
  
  METHODS
  MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, American Society for Clinical Oncology abstracts, and European Society for Medical Oncology abstracts were searched. Randomized clinical trials that compared the efficacy and safety of sorafenib plus chemotherapy in patients with HER2-negative advanced breast cancer with placebo plus chemotherapy were eligible. The endpoints were progression-free survival (PFS), overall survival (OS), time to progression (TTP), duration of response (DOR), overall response rate (ORR), clinical benefits, and adverse effects. The meta-analysis was performed using Review Manager 5.2.6 (The Nordic Cochrane Centre), and the fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1), further analysis (subgroup analysis, sensitivity analysis, or random-effect model) was performed to identify the potential cause. The results are expressed as hazard ratios or risk ratios, with their corresponding 95% confidence intervals.
  
  
  RESULTS
  The final analysis included four trials comprising 844 patients. The results revealed longer PFS and TTP, and higher ORR and clinical benefit rates in patients receiving sorafenib combined with chemotherapy compared to those receiving chemotherapy and placebo. OS and DOR were similar in the two groups. Meanwhile, the incidence of some adverse effects, including hand-foot skin reaction/hand-foot syndrome, diarrhea, rash, and hypertension, were significantly higher in the sorafenib arm.
  
  
  CONCLUSIONS
  Sorafenib combined with chemotherapy may prolong PFS and TTP. This treatment was associated with manageable toxicities, but frequent dose interruptions and reductions were required.
authors.affiliation: Department of Breast and Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Breast and Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Chun-Xiang
authors.initials: CX
authors.lastname: Tian
authors.affiliation: Department of Breast Disease, The Second People's Hospital of Sichuan, Chengdu, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Breast and Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Nan-Sheng
authors.initials: NS
authors.lastname: Cheng
authors.affiliation: Tumor Molecular Laboratory, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Zu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
keywords: Breast neoplasms; Meta-analysis; Sorafenib; Treatment outcome
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