title: Overall and KRAS-specific results of combined cetuximab treatment and chemotherapy for metastatic colorectal cancer: a meta-analysis.
abstract: OBJECTIVE
  This study compared the efficacy and toxicities of cetuximab combined with chemotherapy versus chemotherapy for patients with metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on the outcomes was also investigated.
  
  
  METHODS
  Literature retrieval, trials selection and assessment, data collection, and statistical analysis were performed according to the Cochrane Handbook 5.0.2. The outcome measures were tumor response rate, progression-free survival, overall survival, and adverse effects.
  
  
  RESULTS
  Four randomized controlled trials, comprising totally 2,912 patients, were included. Meta-analysis showed higher response rate (RR 1.93; 95% CI, 1.14-3.26) and significant improvement in progression-free survival (PFS; HR 0.80; 95% CI, 0.67-0.95) in cetuximab-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding overall survival (OS; HR 0.95; 95% CI, 0.87-1.05). In wild-type KRAS patients, treatment with cetuximab plus chemotherapy significantly increased response rate (RR 1.44; 95% CI, 1.20-1.73) and improved PFS (HR 0.64; 95% CI, 0.50-0.84), as compared with chemotherapy groups, but not for OS (HR 0.84; 95% CI, 0.64-1.11). In mutant KRAS patients, there was no significant difference between those treated with cetuximab plus chemotherapy and those with chemotherapy alone regarding response rate (RR 0.81; 95% CI, 0.61-1.08), PFS (HR 1.37; 95% CI, 0.81-2.31), and OS (HR 1.03; 95% CI, 0.74-1.44). The risk of grade 3/4 rash, diarrhea, neutropenia, and fatigue was significantly increased in cetuximab combination groups as compared with chemotherapy groups.
  
  
  CONCLUSIONS
  The use of cetuximab in addition to chemotherapy was a valid alternative for patients with mCRC. Benefit of cetuximab was only limited to patients with wild-type KRAS tumors.
authors.affiliation: Department of Oncology, Tianjin Medical University General Hospital, #154 Anshan Road, Heping District, Tianjin, 300052, China. zllcaroline@163.com
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D006801:Humans; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab