title: A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma.
abstract: BACKGROUND
  A combination of cetuximab and sorafenib in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) were assessed for potential benefit.
  
  
  METHODS
  In a randomized phase II study, R/M HNSCC patients were treated with cetuximab 400mg/m(2) IV on day 1 followed by 250mg/m(2) IV weekly (Arm A), or cetuximab at the same dose/schedule plus sorafenib 400mg PO twice-a-day (Arm B). Each cycle was 21days. Tumor p16 and HPV status, and plasma immunomodulatory cytokine levels were assessed.
  
  
  RESULTS
  Of 55 patients enrolled (Arm A-27, Arm B-28), 52 patients received assigned treatments and 43 were evaluable for response. Overall response rate was 8% for both arms. Median overall survival (OS) and progression-free survival (PFS) were 9.0 and 3.0months in Arm A, and 5.7 and 3.2months in Arm B, respectively. Forty-four patients had tumors available for p16 staining (35-negative, 9-positive). Three of nine p16-positive tumors were also HPV positive. The p16-negative patients had significantly better PFS compared to the p16-positive patients (3.7 vs. 1.6months; p-value: 0.03), regardless of study arms. Twenty-four plasma samples were tested for 12 cytokine levels and patients with higher TGFβ1 levels had inferior PFS compared to lower levels (1.9 vs. 4.7months; adjusted p-value: 0.015), regardless of study arms.
  
  
  CONCLUSIONS
  A subset of R/M patients with p16-negative tumors or lower plasma TGFβ1 levels had longer PFS given the cetuximab-based therapy. However, both arms showed only modest response and sorafenib given with cetuximab did not demonstrate clinical benefit.
authors.affiliation: Vanderbilt University, Nashville, TN, United States. Electronic address: jill.gilbert@vanderbilt.edu.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilbert
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, FL, United States. Electronic address: Michael.Schell@moffitt.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schell
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, FL, United States. Electronic address: Xiuhua.Zhao@moffitt.org.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Vanderbilt University, Nashville, TN, United States. Electronic address: barbara.murphy@Vanderbilt.Edu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Murphy
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, FL, United States. Electronic address: Tawee.Tanvetyanon@moffitt.org.
authors.forename: Tawee
authors.initials: T
authors.lastname: Tanvetyanon
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, FL, United States. Electronic address: Marino.Leon@Moffitt.org.
authors.forename: Marino E
authors.initials: ME
authors.lastname: Leon
authors.affiliation: UNC Lineberger Cancer Center, Chapel Hill, NC, United States. Electronic address: hayes@med.unc.edu.
authors.forename: D
authors.initials: D
authors.lastname: Neil Hayes
authors.affiliation: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, United States. Electronic address: mhaigent@montefiore.org.
authors.forename: Missak
authors.initials: M
authors.lastname: Haigentz
authors.affiliation: Emory Winship Cancer Institute, Atlanta, GA, United States. Electronic address: NFSABA@emory.edu.
authors.forename: Nabil
authors.initials: N
authors.lastname: Saba
authors.affiliation: University of Southern California, Los Angeles, CA, United States. Electronic address: Jorge.Nieva@med.usc.edu.
authors.forename: Jorge
authors.initials: J
authors.lastname: Nieva
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: jbishop@jhmi.edu.
authors.forename: Justin
authors.initials: J
authors.lastname: Bishop
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: dsidrans@jhmi.edu.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: ravira@jhmi.edu.
authors.forename: Rajani
authors.initials: R
authors.lastname: Ravi
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: abedi1@jhmi.edu.
authors.forename: Atul
authors.initials: A
authors.lastname: Bedi
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, MD, United States. Electronic address: cchung11@jhmi.edu.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D000068818:Cetuximab / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D012008:Recurrence; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D000068818:Cetuximab
keywords: Cetuximab; Head and neck squamous cell carcinoma; Metastasis; Phase II trial; Recurrence; Response; Sorafenib; TGFβ1; Toxicity; p16