title: Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial.
abstract: In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years.
  
  
  
  Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed.
  
  
  
  Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups.
  
  
  
  Advancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients.
  
  
  
  NCT01345682 (ClinicalTrials.gov).
authors.affiliation: Department of Oncology, KU Leuven, Leuven Department of General Medical Oncology, UZ Leuven, Leuven, Belgium paul.clement@uzleuven.be.
authors.forename: P M
authors.initials: PM
authors.lastname: Clement
authors.affiliation: Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, Essen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gauler
authors.affiliation: Institut Roi Albert II, Service d'Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Machiels
authors.affiliation: Departmant of Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School, Boston, USA.
authors.forename: R I
authors.initials: RI
authors.lastname: Haddad
authors.affiliation: Departmant of Medical Oncology, Léon Bérard Center, University of Lyon, Lyon, France.
authors.forename: J
authors.initials: J
authors.lastname: Fayette
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: L F
authors.initials: LF
authors.lastname: Licitra
authors.affiliation: Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tahara
authors.affiliation: Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, USA.
authors.forename: E E W
authors.initials: EE
authors.lastname: Cohen
authors.affiliation: Service d'Oncologie Médicale, Institut du Cancer de Montpellier Val d'Aurelle, Montpellier, France.
authors.forename: D
authors.initials: D
authors.lastname: Cupissol
authors.affiliation: Department of Medical Oncology, Hospital Clínic and University of Barcelona, Barcelona, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Grau
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif Centre Antoine Lacassagne, Nice, France.
authors.forename: J
authors.initials: J
authors.lastname: Guigay
authors.affiliation: Department of Melanoma, Soft Tissues, Muscolo Scheletal, Head and Neck, Head and Neck Medical Oncology, National Tumor Institute of Naples, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Caponigro
authors.affiliation: Oncologia Clinica, Instituto do Câncer do Estado de São Paulo, São Paulo.
authors.forename: G
authors.initials: G
authors.lastname: de Castro
authors.affiliation: Department of Medical Oncology, Hospital de Câncer de Barretos, São Paulo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: de Souza Viana
authors.affiliation: Charité Comprehensive Cancer Center, Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
authors.affiliation: Department of Medical Oncology, Hospital Universitario Vall D'Hebron, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Del Campo
authors.affiliation: Biometrics and Data Management, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, USA.
authors.forename: X J
authors.initials: XJ
authors.lastname: Cong
authors.affiliation: Division of Oncology, Boehringer Ingelheim Danmark A/S, Copenhagen, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Ehrnrooth
authors.affiliation: Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
mesh_terms: D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D010984:Platinum / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D000077716:Afatinib; D010984:Platinum; D008727:Methotrexate
keywords: HNSCC; afatinib; methotrexate; older; phase III; second-line