title: Predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a meta-analysis.
abstract: OBJECTIVE
  This study aimed to evaluate the predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs).
  
  
  METHODS
  Computer searches of the literature on BRAF mutation in mCRC patients were performed. Studies with objective response rate (ORR) to anti-EGFR MoAbs and/or overall survival (OS) and progression-free survival (PFS) with different BRAF gene expression in mCRC patients were eligible.
  
  
  RESULTS
  A total of 19 studies including 2875 patients was enrolled in the meta-analysis. BRAF mutation was detected in 246 patients. The ORR was 18.4% (40/217) in mutant BRAF group and 41.7% (831/1993) in the wild-type BRAF group. The overall risk ratio (RR) for the ORR of BRAF mutation patients compared with wild-type BRAF patients was 0.58 (95% confidence intervals [CI] 0.35-0.94, P = 0.027). The median PFS of patients with BRAF mutation was significantly shorter than that of patients with wild-type BRAF (hazard ratio [HR] 2.98, 95% CI 2.07-4.27, P < 0.001) and the median OS of patients with BRAF mutation was also significantly shorter than that of those with wild-type BRAF (HR 2.85, 95% CI 2.31-3.52, P < 0.001).
  
  
  CONCLUSIONS
  BRAF mutation is associated with poor response to anti-EGFR MoAbs and it is an adverse prognostic biomarker of the survival of patients with mCRC.
authors.affiliation: Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.forename: An Tao
authors.initials: AT
authors.lastname: Xu
authors.forename: Ming Ming
authors.initials: MM
authors.lastname: Zhu
authors.forename: Jin Lu
authors.initials: JL
authors.lastname: Tong
authors.forename: Xi Tao
authors.initials: XT
authors.lastname: Xu
authors.forename: Zhi Hua
authors.initials: ZH
authors.lastname: Ran
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: colorectal neoplasms; epidermal growth factor receptor; human BRAF protein; meta-analysis; monoclonal antibodies; mutation