title: A phase II trial of dacomitinib, an oral pan-human EGF receptor (HER) inhibitor, as first-line treatment in recurrent and/or metastatic squamous-cell carcinoma of the head and neck.
abstract: BACKGROUND
  An open-label, multicenter, single-arm phase II trial was conducted to investigate the clinical activity of dacomitinib in recurrent/metastatic squamous-cell carcinoma of the head and neck (RM-SCCHN).
  
  
  METHODS
  Eligible patients were administered dacomitinib at 45 mg orally daily, in 21-day cycles. Primary end point was objective response rate.
  
  
  RESULTS
  Sixty-nine patients were enrolled with a median age of 62 years. Among response-evaluable patients, 8 [12.7%, 95% confidence interval (CI) 5.6% to 23.5%] achieved a partial response and 36 (57.1%) had stable disease, lasting ≥24 weeks in 9 patients (14.3%). The median progression-free survival (PFS) was 12.1 weeks and the median overall survival (OS) was 34.6 weeks. Most adverse events (AEs) were tolerable. The most common grade 3 or higher treatment-related AEs were diarrhea (15.9%), acneiform dermatitis (8.7%), and fatigue (8.7%). Treatment-related AEs led to at least one dose interruption in 28 (40.6%) patients and dose reductions in 26 (37.7%). Permanent treatment discontinuation occurred in 8 (11.6%) patients due to treatment-related AEs.
  
  
  CONCLUSIONS
  Dacomitinib demonstrated clinical activity in RM-SCCHN, and the primary end point of this study was met. The toxicity profile of this agent was generally manageable with dose interruptions and adjustments.
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital,  University of Toronto, Toronto.
authors.forename: A R
authors.initials: AR
authors.lastname: Abdul Razak
authors.forename: D
authors.initials: D
authors.lastname: Soulières
authors.forename: S A
authors.initials: SA
authors.lastname: Laurie
authors.forename: S J
authors.initials: SJ
authors.lastname: Hotte
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: E
authors.initials: E
authors.lastname: Winquist
authors.forename: S
authors.initials: S
authors.lastname: Chia
authors.forename: C
authors.initials: C
authors.lastname: Le Tourneau
authors.forename: P-F
authors.initials: PF
authors.lastname: Nguyen-Tan
authors.forename: E X
authors.initials: EX
authors.lastname: Chen
authors.forename: K K
authors.initials: KK
authors.lastname: Chan
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Giri
authors.forename: C
authors.initials: C
authors.lastname: Mormont
authors.forename: S
authors.initials: S
authors.lastname: Quinn
authors.forename: L L
authors.initials: LL
authors.lastname: Siu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D003967:Diarrhea / Q000139:chemically induced; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D052999:Quinazolinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D052999:Quinazolinones; C525726:dacomitinib; D066246:ErbB Receptors