title: Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a randomized, double-blind safety study comparing cetuximab produced from two manufacturing processes using the EXTREME study regimen.
abstract: BACKGROUND
  Cetuximab, in combination with platinum chemotherapy plus 5-fluoruracil (5-FU), is approved for the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Cetuximab manufactured by ImClone (US commercial cetuximab) potentially results in higher systemic exposures than cetuximab manufactured by Boehringer Ingelheim (BI-manufactured cetuximab). This prospective, randomized, double-blind study compared the safety profiles of the two cetuximab formulations.
  
  
  METHODS
  Patients with previously untreated locoregionally recurrent and/or metastatic SCCHN were randomly assigned to receive the same dose of US commercial cetuximab (Arm A) or BI-manufactured cetuximab (Arm B), each in combination with cisplatin or carboplatin plus 5-FU. The primary outcome was all-grade, all-cause treatment-emergent adverse events (TEAEs).
  
  
  RESULTS
  The majority of patients experienced ≥ 1 TEAE, regardless of causality (Arm A: 75/77 patients, 97.4%; Arm B: 68/71 patients, 95.8%). TEAEs with the highest incidence included nausea, fatigue, and hypomagnesemia in both arms. The absolute risk difference between the two arms for patients experiencing at least one adverse event (AE) was 0.029 (p = 0.281, 95% confidence interval [CI]: -0.024, 0.082) for AEs regardless of causality and 0.005 (p = 0.915, 95% CI: -0.092, 0.103) for AEs possibly related to study drug. There were no significant differences between the two arms in the incidence of acneiform rash, cardiac events, infusion reactions, or hypomagnesemia. Overall survival, progression-free survival, and overall response rates were similar in the two arms.
  
  
  CONCLUSIONS
  There were no clinically meaningful differences in safety between US commercial cetuximab and BI-manufactured cetuximab in combination with platinum-based therapy with 5-FU in patients with locoregionally recurrent and/or metastatic SCCHN. The use of US commercial cetuximab in this combination chemotherapy regimen did not result in any unexpected safety signals. The efficacy results of this study are consistent with the efficacy results of the cetuximab arm of the EXTREME study.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01081041 ; date of registration: March 3, 2010).
authors.affiliation: Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Soulières
authors.affiliation: Instituto Nacional de Cancerologia, Mexico City, Mexico.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Aguilar
authors.affiliation: Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Chen
authors.affiliation: Mount Sinai School of Medicine Tisch Cancer Institute, New York, NY, USA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Misiukiewicz
authors.affiliation: London Regional Cancer Center, London, Ontario, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Ernst
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Bryant
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: He
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Chin
authors.affiliation: Washington University School of Medicine, 660 S. Euclid, Box 8056, St. Louis, MO, 63110, USA. dadkins@dom.wustl.edu.
authors.forename: Douglas
authors.initials: D
authors.lastname: Adkins
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D000068818:Cetuximab / Q000008:administration & dosage* / Q000009:adverse effects; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010984:Platinum / Q000008:administration & dosage; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D010984:Platinum; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil