title: Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: rationale for future randomised trials in human papilloma virus-negative disease.
abstract: BACKGROUND
  This randomised Phase II study assessed the activity and safety of concurrent chemoradiotherapy (CRT) and lapatinib followed by maintenance treatment in locally advanced, unresected stage III/IVA/IVB head and neck cancer.
  
  
  METHODS
  Patients were randomised 1:1 to concurrent CRT and placebo followed by placebo or concurrent CRT and lapatinib followed by lapatinib. Treatment continued until disease progression or study withdrawal. Primary end-point was complete response rate (CRR) by independent review 6 months post-CRT.
  
  
  RESULTS
  Sixty-seven patients (median age 56 years; 97% Eastern Cooperative Oncology Group performance status ≤1; 82% stage IV) were recruited. CRT dose intensities were unaffected by lapatinib: median radiation dose 70 Gy (lapatinib, placebo), duration 49 (lapatinib) and 50 days (placebo); median cisplatin dose 260 mg/m(2) (lapatinib) and 280 mg/m(2) (placebo). Lapatinib combined with CRT was well-tolerated. Grade 3/4 toxicities during CRT were balanced between arms, with the exception of an excess of grade 3 diarrhoea (6% versus 0%) and rash (9% versus 3%) and two grade 4 cardiac events in the lapatinib arm. CRR at 6 months post-CRT was 53% with lapatinib versus 36% with placebo in the intent-to-treat population. The progression-free survival (PFS) and overall survival rates at 18 months were 55% versus 41% and 68% versus 57% for the lapatinib and placebo arms, respectively. The difference between study arms was greatest in p16-negative disease (median PFS >20.4 months [lapatinib] versus 10.9 [placebo]).
  
  
  CONCLUSIONS
  Lapatinib combined with CRT is well-tolerated with numeric increases in CRR at 6 months post-CRT and median PFS in p16-negative disease.
authors.affiliation: Royal Marsden Hospital, London, UK. kevin.harrington@icr.ac.uk
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.forename: Alain
authors.initials: A
authors.lastname: Berrier
authors.forename: Martin
authors.initials: M
authors.lastname: Robinson
authors.forename: Eva
authors.initials: E
authors.lastname: Remenar
authors.forename: Martin
authors.initials: M
authors.lastname: Housset
authors.forename: Fernando Hurtado
authors.initials: FH
authors.lastname: de Mendoza
authors.forename: Jérôme
authors.initials: J
authors.lastname: Fayette
authors.forename: Hisham
authors.initials: H
authors.lastname: Mehanna
authors.forename: Iman
authors.initials: I
authors.lastname: El-Hariry
authors.forename: Natalie
authors.initials: N
authors.lastname: Compton
authors.forename: Natalie
authors.initials: N
authors.lastname: Franklin
authors.forename: Nigel
authors.initials: N
authors.lastname: Biswas-Baldwin
authors.forename: Mike
authors.initials: M
authors.lastname: Lau
authors.forename: Philippe
authors.initials: P
authors.lastname: Legenne
authors.forename: Rejnish
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D003967:Diarrhea / Q000209:etiology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000032:analysis; D005076:Exanthema / Q000209:etiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000502:physiology; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D016896:Treatment Outcome
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D011799:Quinazolines; D000077341:Lapatinib; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin