title: Infectious complications in cancer patients treated with anti-EGFR monoclonal antibodies cetuximab and panitumumab: a systematic review and meta-analysis.
abstract: BACKGROUND
  Clinical trials have reported a substantial variation in the risk of infection related to anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab. We performed a systematic review and meta-analysis to assess the infection risk in cancer patients treated with anti-EGFR mAbs.
  
  
  METHODS
  We searched PubMed and the ASCO online database of meeting abstracts up to January 2014 for relevant clinical trials. Eligible studies included randomized controlled trials (RCTs) of cetuximab and panitumumab that reported adequate safety data for grade 3-4 infection or febrile neutropenia (FN). The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated.
  
  
  RESULTS
  A total of 14,957 patients from 28 trials were included. Treatment with anti-EGFR mAbs was associated with an increased risk of high-grade infection (RR, 1.49; 95% CI, 1.33-1.66; P<0.001) and FN (RR, 1.27; 95% CI, 1.09-1.48; P=0.002). The incidence of high-grade infection and FN due to anti-EGFR mAbs was 9.3% (95% CI, 7.2-12.0%) and 5.3% (95% CI, 3.3-8.3%), respectively. A significantly increased risk of high-grade infection was observed in all subgroups analyses (type of anti-EGFR mAb, therapy of control arm and duration of treatment) except for tumor type (only colorectal cancer and non-small cell lung cancer (NSCLC) groups had the increased risk). Subgroup analyses revealed a significantly increased risk of FN in the following subgroups: cetuximab, NSCLC and treatment duration longer than the median of all trials (3.1months).
  
  
  CONCLUSIONS
  The use of anti-EGFR mAbs is associated with a significantly higher risk of high-grade infection and febrile neutropenia.
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, 170 Manning Drive, CB# 7305, Chapel Hill, NC 27599, USA. Electronic address: tomohiro.funakoshi@unchealth.unc.edu.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Funakoshi
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Division of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University Hospital, Fukuoka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D064147:Febrile Neutropenia / Q000139:chemically induced; D006801:Humans; D007239:Infections / Q000453:epidemiology*; D000077544:Panitumumab; D012307:Risk Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Anti-EGFR monoclonal antibody; Cetuximab; Febrile neutropenia; Infection; Meta-analysis; Panitumumab; Systematic review