title: Neoadjuvant Bevacizumab plus Chemotherapy versus Chemotherapy Alone to Treat Non-Metastatic Breast Cancer: A Meta-Analysis of Randomised Controlled Trials.
abstract: OBJECTIVE
  Results from previous randomised controlled trials (RCTs) investigating whether the addition of bevacizumab to neoadjuvant chemotherapy (NAC) could statistically significantly increase the pathological complete response (pCR) and to identify which subgroup would benefit most from such regimens have produced conflicting results. This meta-analysis was designed to assess the efficacy and safety of bevacizumab plus chemotherapy compared with chemotherapy alone in the neoadjuvant setting.
  
  
  METHODS
  A literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane library was performed to identify eligible studies. The primary endpoint of interest was pCR. The secondary endpoints were clinical complete rate (cCR), surgery rate, breast-conserving surgery (BCS) rate, and toxicity. The meta-analysis was performed using Review Manager software version 5.3.
  
  
  RESULTS
  Nine RCTs matched the selection criteria, yielding a total of 4967 patients (bevacizumab plus chemotherapy: 50.1%, chemotherapy alone: 49.9%). The results of this meta-analysis demonstrated that the addition of bevacizumab to NAC significantly increased the pCR rate (odds ratio [OR] = 1.34 [1.18-1.54]; P < 0.0001) compared with chemotherapy alone. Subgroup analysis showed that the effect of bevacizumab was more pronounced in patients with HER2-negative cancer (OR = 1.34 [1.17-1.54]; P < 0.0001) compared with HER2-positive cancer (OR = 1.69 [0.90-3.20]; P = 0.11). Similarly, in patients with HER2-negative cancer, the effect of bevacizumab was also more pronounced in patients with HR-negative cancer (OR = 1.38 [1.09-1.74]; P = 0.007) compared with HR-positive cancer (OR = 1.36 [0.78-2.35]; P = 0.27). No significant differences were observed between the groups with respect to cCR, surgery rate, or BCS rate. Additionally bevacizumab was associated with a higher incidence of neutropenia, febrile neutropenia, and hand-foot syndrome.
  
  
  CONCLUSIONS
  Higher proportions of patients achieved pCR when bevacizumab was added to NAC compared with when they received chemotherapy alone; acceptable toxicities were also found. Subgroup analysis demonstrated that patients with histologically confirmed HER2-negative and HR-negative breast cancer benefited the most.
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Guang-yu
authors.initials: GY
authors.lastname: Yao
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Min-feng
authors.initials: MF
authors.lastname: Liu
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Lu-jia
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Hu
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Chang-sheng
authors.initials: CS
authors.lastname: Ye
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental / Q000379:methods; D020360:Neoadjuvant Therapy / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D018719:Erb-b2 Receptor Tyrosine Kinases