title: Effect of RAS status on anti-EGFR monoclonal antibodies + 5-FU infusion-based chemotherapy in first-line treatment of metastatic colorectal cancer: A meta-analysis.
abstract: OBJECTIVE
  To investigate the effect of RAS on anti-EGFR moAb + 5-FU infusion based chemotherapy in first-line treatment of mCRC.
  
  
  METHODS
  The MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane databases and ClinicalTrials.gov databases were independently reviewed. Primary end points included overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities. Correlation between RAS status and PFS, OS, ORR or toxicities was expressed as a hazard ratio (HR) or relative risk (RR).
  
  
  RESULTS
  KRAS exon 2 wild-type (-wt) mCRC benefited from adding anti-EGFR moAb (compared with chemotherapy alone: OS: HR 0.88, P = 0.008; PFS: HR 0.74, P < 0.001; ORR: RR 1.34, P = 0.003. Compared with Bevacizumab: OS: HR 0.83, P = 0.003). KRAS exon 2-wt but other RAS mutations mCRC did not benefit from adding anti-EGFR moAb. RAS-wt mCRC benefited from adding anti-EGFR moAb (compared with chemotherapy alone: OS: HR: 0.75, P < 0.001; PFS: HR 0.65, P < 0.001; ORR: RR 1.51, P = 0.020. Compared with Bevacizumab: OS: HR 0.79, P = 0.002). KRAS exon 2-wt but BRAF mutation mCRC did not benefit from adding anti-EGFR moAb. Subgroup analysis suggested that anti-EGFR moAb prolonged PFS for male, liver metastasis-only, ECOG 0-1, and colon primary site groups. Anti-EGFR moAb increased controllable grade 3-4 toxicities including rash, diarrhea, and anemia.
  
  
  CONCLUSIONS
  Adding anti-EGFR moAb as first-line treatment in RAS-wt mCRC prolonged OS. Whether BRAF mutation is a predictive marker to anti-EGFR moAb is not clear.
authors.affiliation: Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, PR China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Kezuo
authors.initials: K
authors.lastname: Hou
authors.affiliation: Department of Clinical Epidemiology and Evidence Based Medicine, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Jinglei
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, PR China.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Zhang
keywords: First-line treatment; Meta-analysis; Metastatic colorectal cancer; Monoclonal antibodies; Ras mutation