title: KRAS status and resistance to epidermal growth factor receptor tyrosine-kinase inhibitor treatment in patients with metastatic colorectal cancer: a meta-analysis.
abstract: OBJECTIVE
  This study reviewed the association between KRAS mutation and resistance to treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) in patients with metastatic colorectal cancer (mCRC).
  
  
  METHODS
  A search was carried out of PubMed, MEDLINE, EMBASE and the Cochrane Library databases (to November 2013) without language restrictions.
  
  
  RESULTS
  Ten studies were included in the final meta-analysis, consisting of 1339 patients with mCRC, of whom 427 (32%) had a KRAS mutation. The objective response rate (ORR) of mCRC patients with KRAS mutation was 8% (33/427), whereas the ORR of mCRC patients with wild-type KRAS was 34% (306/912). The overall pooled response rate (RR) for the ORR was 1.297 (95% CI 1.244-1.353, P < 0.01). Subgroup analysis comparing cetuximab monotherapy treatment with cetuximab plus chemotherapy, showed a pooled RR of 1.26 (95% CI 1.12-0.63, P < 0.01) and 1.30 (95% CI 1.25-1.36, P < 0.01), respectively. For patients receiving anti-EGFR with monoclonal antibodies (mAb) given as first-line treatment or not, the pooled RRs were 1.34 (95% CI 1.23-1.46, P < 0.01) and 1.29 (95% CI 1.23-1.35, P < 0.01). The data on progression-free survival from five studies in the meta-analysis gave a hazard ratio (HR) of 1.99 with a 95% CI of 1.69-2.29. Finally, the data for overall survival in mCRC patients were pooled from the only three studies reporting the HR (1.80; 95% CI 1.50-2.10). None of the results had any evidence of heterogeneity.
  
  
  CONCLUSIONS
  All the results favoured a stronger link between mutant KRAS and anti-EGFR mAb, but due to a mutually exclusive relationship between KRAS and other gene mutations the clinical usefulness of KRAS mutation as a selection marker for sensitivity to EGFR TKIs in mCRC is limited.
authors.affiliation: Oncology Department, Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai TCM University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Shi
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Hou
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab
keywords: EGFR TKIs; KRAS; colorectal cancer; meta-analysis