title: Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma: A Randomized Clinical Trial.
abstract: OBJECTIVE
  The Canadian Cancer Trials Group study HN.6 is the largest randomized clinical trial to date comparing the concurrent administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies with radiotherapy (RT) to standard chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).
  
  
  OBJECTIVE
  To compare progression-free survival (PFS) in patients with LA-SCCHN treated with standard-fractionation RT plus high-dose cisplatin vs accelerated-fractionation RT plus the anti-EGFR antibody panitumumab.
  
  
  METHODS
  A randomized phase 3 clinical trial in 17 Canadian centers. A total of 320 patients were randomized between December 2008 and November 2011.
  
  
  METHODS
  Patients with TanyN+M0 or T3-4N0M0 LA-SCCHN were randomized 1:1 to receive standard-fractionation RT (70 Gy/35 over 7 weeks) plus cisplatin at 100 mg/m2 intravenous for 3 doses (arm A) vs accelerated-fractionation RT (70 Gy/35 over 6 weeks) plus panitumumab at 9 mg/kg intravenous for 3 doses (arm B).
  
  
  METHODS
  Primary end point was PFS. Due to an observed declining event rate, the protocol was amended to a time-based analysis. Secondary end points included overall survival, local and regional PFS, distant metastasis-free survival, quality of life, adverse events, and safety.
  
  
  RESULTS
  Of 320 patients randomized (268 [84%] male; median age, 56 years), 156 received arm A and 159 arm B. A total of 93 PFS events occurred. By intention-to-treat, 2-year PFS was 73% (95% CI, 65%-79%) in arm A and 76% (95% CI, 68%-82%) in arm B (hazard ratio [HR], 0.95; 95% CI, 0.60-1.50; P = .83). The upper bound of the HR 95% CI exceeded the prespecified noninferiority margin. Two-year overall survival was 85% (95% CI, 78%-90%) in arm A and 88% (95% CI, 82%-92%) in arm B (HR, 0.89; 95% CI, 0.54-1.48; P = .66). Incidence of any grade 3 to 5 nonhematologic adverse event was 88% in arm A and 92% in arm B (P = .25).
  
  
  CONCLUSIONS
  With a median follow-up of 46 months, the PFS of panitumumab plus accelerated-fractionation RT was not superior to cisplatin plus standard-fractionation RT in LA-SCCHN and noninferiority was not proven. Despite having negative results, HN.6 has contributed important data regarding disease control and toxic effects of these treatment strategies.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00820248.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John N
authors.initials: JN
authors.lastname: Waldron
authors.affiliation: Canadian Cancer Trials Group, Kingston, Ontario, Canada.
authors.forename: Bingshu E
authors.initials: BE
authors.lastname: Chen
authors.affiliation: London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.affiliation: Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Jim R
authors.initials: JR
authors.lastname: Wright
authors.affiliation: Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Abdenour
authors.initials: A
authors.lastname: Nabid
authors.affiliation: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: John H
authors.initials: JH
authors.lastname: Hay
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Queen's University, Kingston, Ontario, Canada.
authors.forename: Ana
authors.initials: A
authors.lastname: Johnson
authors.affiliation: McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Shenouda
authors.affiliation: Ottawa Hospital Cancer Centre, Ottawa, Ottawa, Ontario, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Chasen
authors.affiliation: Northeast Cancer Centre, Sudbury, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pearce
authors.affiliation: Cancer Care Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: James B
authors.initials: JB
authors.lastname: Butler
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Breen
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eric Xueyu
authors.initials: EX
authors.lastname: Chen
authors.affiliation: Quality Assurance Review Centre, Providence, Rhode Island.
authors.forename: T J
authors.initials: TJ
authors.lastname: FitzGerald
authors.affiliation: Queen's University, Kingston, Ontario, Canada.
authors.forename: T J
authors.initials: TJ
authors.lastname: Childs
authors.affiliation: Canadian Cancer Trials Group, Kingston, Ontario, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Montenegro
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.affiliation: Canadian Cancer Trials Group, Kingston, Ontario, Canada.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Parulekar