title: Rationale and design of LUX-Head & Neck 1: a randomised, Phase III trial of afatinib versus methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma who progressed after platinum-based therapy.
abstract: BACKGROUND
  Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) receiving platinum-based chemotherapy as their first-line treatment have a dismal prognosis, with a median overall survival (OS) of ~7 months. Methotrexate is sometimes used following platinum failure or in patients not fit enough for platinum therapy, but this agent has not demonstrated any OS improvement. Targeted therapies are a novel approach, with the EGFR-targeting monoclonal antibody cetuximab (plus platinum-based chemotherapy) approved in the US and Europe in the first-line R/M setting, and as monotherapy following platinum failure in the US. However, there is still a high unmet medical need for new treatments that improve outcomes in the second-line R/M setting following failure on first-line platinum-containing regimens. Afatinib, an irreversible ErbB family blocker, was recently approved for the first-line treatment of EGFR mutation-positive metastatic non-small cell lung cancer. Afatinib has also shown clinical activity similar to cetuximab in a Phase II proof-of-concept HNSCC trial. Based on these observations, the Phase III, LUX-Head & Neck 1 study is evaluating afatinib versus methotrexate in R/M HNSCC patients following progression on platinum-based chemotherapy in the R/M setting.
  
  
  METHODS
  Patients with progressive disease after one first-line platinum-based chemotherapy are randomised 2:1 to oral afatinib (starting dose 40 mg once daily) or IV methotrexate (starting dose 40 mg/m(2) once weekly) administered as monotherapy with best supportive care until progression or intolerable adverse events. Efficacy of afatinib versus methotrexate will be assessed in terms of progression-free survival (primary endpoint). Disease progression will be evaluated according to RECIST v1.1 by investigator and independent central review. Secondary endpoints include OS, tumour response and safety. Health-related quality of life and biomarker assessments will also be performed.
  
  
  CONCLUSIONS
  If the LUX-Head & Neck 1 trial meets its primary endpoint, it will demonstrate the ability of afatinib to elicit an improved treatment benefit versus a commonly used chemotherapy agent in the second-line treatment of R/M HNSCC patients who have failed on first-line platinum-based therapy, confirm the clinical efficacy of afatinib observed in the Phase II proof-of-concept study, and establish a new standard of care for this patient population.
authors: Cancer Center, Service d'Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium. jean-pascal.machiels@uclouvain.be.
authors: Jean-Pascal H
authors: JP
authors: Machiels
authors: Lisa F
authors: LF
authors: Licitra
authors: Robert I
authors: RI
authors: Haddad
authors: Makoto
authors: M
authors: Tahara
authors: Ezra Ew
authors: EE
authors: Cohen
mesh_terms: D000077716:Afatinib; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002985:Clinical Protocols; D018450:Disease Progression; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D010984:Platinum / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D019233:Retreatment; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D011799:Quinazolines; D000077716:Afatinib; D010984:Platinum; D008727:Methotrexate