title: Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer.
abstract: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation.
  
  
  
  Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%.
  
  
  
  110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients.
  
  
  
  The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation.
authors: Departments of Medicine, University of Chicago, Chicago, Illinois. Electronic address: tseiwert@medicine.bsd.uchicago.edu.
authors: Tanguy Y
authors: TY
authors: Seiwert
authors: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors: James M
authors: JM
authors: Melotek
authors: Department of Otolaryngology, University of Chicago, Chicago, Illinois.
authors: Elizabeth A
authors: EA
authors: Blair
authors: Department of Otolaryngology, Rush University, Chicago, Illinois.
authors: Kerstin M
authors: KM
authors: Stenson
authors: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors: Joseph K
authors: JK
authors: Salama
authors: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors: Mary Ellyn
authors: ME
authors: Witt
authors: Departments of Medicine, University of Chicago, Chicago, Illinois.
authors: Ryan J
authors: RJ
authors: Brisson
authors: Departments of Medicine, University of Chicago, Chicago, Illinois.
authors: Apoorva
authors: A
authors: Chawla
authors: Departments of Medicine, University of Chicago, Chicago, Illinois.
authors: Allison
authors: A
authors: Dekker
authors: Department of Pathology, University of Chicago, Chicago, Illinois.
authors: Mark W
authors: MW
authors: Lingen
authors: Department of Public Health Sciences, University of Chicago, Chicago, Illinois.
authors: Masha
authors: M
authors: Kocherginsky
authors: Departments of Medicine, University of Chicago, Chicago, Illinois.
authors: Victoria M
authors: VM
authors: Villaflor
authors: Moores Cancer Center, University of California, San Diego, San Diego, California.
authors: Ezra E W
authors: EE
authors: Cohen
authors: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors: Daniel J
authors: DJ
authors: Haraf
authors: Departments of Medicine, University of Chicago, Chicago, Illinois.
authors: Everett E
authors: EE
authors: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D000068818:Cetuximab / Q000008:administration & dosage*; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000068818:Cetuximab