title: Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer.
abstract: OBJECTIVE
  Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy.
  
  
  METHODS
  The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints.
  
  
  RESULTS
  The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint.
  
  
  CONCLUSIONS
  The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.
authors: Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Montpellier, France. Electronic address: jl-pujol@chu-montpellier.fr.
authors: Jean-Louis
authors: JL
authors: Pujol
authors: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors: Robert
authors: R
authors: Pirker
authors: Smilow Cancer Hospital, Yale Cancer Center, New Haven, CT, United States.
authors: Thomas J
authors: TJ
authors: Lynch
authors: Cross Cancer Center, Edmonton, Alberta, Canada.
authors: Charles A
authors: CA
authors: Butts
authors: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
authors: Rafael
authors: R
authors: Rosell
authors: University Health Network, Princess Margaret Hospital Site, University of Toronto, Toronto, Ontario, Canada.
authors: Frances A
authors: FA
authors: Shepherd
authors: University Hospital Gasthuisberg, KU Leuven, Belgium.
authors: Johan
authors: J
authors: Vansteenkiste
authors: St James's Hospital, Dublin, Ireland.
authors: Kenneth J
authors: KJ
authors: O'Byrne
authors: Merck KGaA, Darmstadt, Germany.
authors: Barbara
authors: B
authors: de Blas
authors: Cancer Communications and Consultancy Ltd., Knutsford, Cheshire, UK.
authors: Jim
authors: J
authors: Heighway
authors: Merck KGaA, Darmstadt, Germany.
authors: Anja
authors: A
authors: von Heydebreck
authors: Christie Hospital NHS Trust, Manchester, UK.
authors: Nick
authors: N
authors: Thatcher
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D000068818:Cetuximab; D004358:Drug Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab
keywords: Cetuximab; Chemotherapy; First-line; Meta-analysis; NSCLC; Tumor