title: Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial.
abstract: BACKGROUND
  Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck.
  
  
  METHODS
  In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760.
  
  
  RESULTS
  Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group.
  
  
  CONCLUSIONS
  In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed.
  
  
  BACKGROUND
  Amgen.
authors.affiliation: Institut Catala d'Oncologia (ICO)-L'Hospitalet, Barcelona, Spain. Electronic address: rmesia@iconcologia.net.
authors.forename: Ricard
authors.initials: R
authors.lastname: Mesía
authors.affiliation: Strahlenheilkunde Universitätsklinikum, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Henke
authors.affiliation: Centre Hospitalier Universitaire de Quebec-Hotel-Dieu de Quebec, Quebec, QC, Canada.
authors.forename: Andre
authors.initials: A
authors.lastname: Fortin
authors.affiliation: Turku University Hospital Department of Oncology and Radiotherapy, Turku, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Minn
authors.affiliation: Unidad de Oncología Servicios de Salud del Estado de Puebla, Puebla, Mexico.
authors.forename: Alejandro Cesar
authors.initials: AC
authors.lastname: Yunes Ancona
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Cmelak
authors.affiliation: University of Texas, Medical Branch, Galveston, TX, USA.
authors.forename: Avi B
authors.initials: AB
authors.lastname: Markowitz
authors.affiliation: Juravinski Cancer Centre, Hamilton, ON, Canada.
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hotte
authors.affiliation: Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada.
authors.forename: Simron
authors.initials: S
authors.lastname: Singh
authors.affiliation: State Key Laboratory in Oncology in South China, The Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Oncologia Medica ASOS Croce E Carle, Cuneo, Italy.
authors.forename: Marco C
authors.initials: MC
authors.lastname: Merlano
authors.affiliation: Centrum Onkologii Instytut M Sklodowskiej-Curie, Gliwice, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Skladowski
authors.affiliation: Amgen, Thousand Oaks, CA, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Amgen, Thousand Oaks, CA, USA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Oliner
authors.affiliation: Amgen, Thousand Oaks, CA, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: VanderWalde
authors.affiliation: Hospital Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Giralt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007390:International Agencies; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000077544:Panitumumab; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D002945:Cisplatin