title: Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522.
abstract: OBJECTIVE
  Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS).
  
  
  METHODS
  Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers.
  
  
  RESULTS
  Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v. 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v. 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v. 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v. 2.0%, respectively; P = .81), 3-year PFS (61.2% v. 58.9%, respectively; P = .76), 3-year OS (72.9% v. 75.8%, respectively; P = .32), locoregional failure (19.9% v. 25.9%, respectively; P = .97), or distant metastasis (13.0% v. 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v. 49.2%, respectively; P < .001) and OS (85.6% v. 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome.
  
  
  CONCLUSIONS
  Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression.
authors.forename: K Kian
authors.initials: KK
authors.lastname: Ang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: David I
authors.initials: DI
authors.lastname: Rosenthal
authors.forename: Phuc Felix
authors.initials: PF
authors.lastname: Nguyen-Tan
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sherman
authors.forename: Randal S
authors.initials: RS
authors.lastname: Weber
authors.forename: James M
authors.initials: JM
authors.lastname: Galvin
authors.forename: James A
authors.initials: JA
authors.lastname: Bonner
authors.forename: Jonathan
authors.initials: J
authors.lastname: Harris
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
authors.forename: Richard C
authors.initials: RC
authors.lastname: Jordan
authors.forename: Andre A
authors.initials: AA
authors.lastname: Konski
authors.forename: Wade L
authors.initials: WL
authors.lastname: Thorstad
authors.forename: Andy
authors.initials: A
authors.lastname: Trotti
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Beitler
authors.forename: Adam S
authors.initials: AS
authors.lastname: Garden
authors.forename: William J
authors.initials: WJ
authors.lastname: Spanos
authors.forename: Sue S
authors.initials: SS
authors.lastname: Yom
authors.forename: Rita S
authors.initials: RS
authors.lastname: Axelrod
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000068818:Cetuximab; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009367:Neoplasm Staging; D018579:Patient Selection; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011838:Radiation-Sensitizing Agents; D000068818:Cetuximab; D002945:Cisplatin