PMID- 31450171
OWN - NLM
STAT- MEDLINE
DCOM- 20200630
LR  - 20200630
IS  - 1879-0593 (Electronic)
IS  - 1368-8375 (Linking)
VI  - 97
DP  - 2019 Oct
TI  - Afatinib as second-line treatment in patients with recurrent/metastatic squamous 
      cell carcinoma of the head and neck: Subgroup analyses of treatment adherence, 
      safety and mode of afatinib administration in the LUX-Head and Neck 1 trial.
PG  - 82-91
LID - S1368-8375(19)30269-6 [pii]
LID - 10.1016/j.oraloncology.2019.08.004 [doi]
AB  - OBJECTIVES: Patients with head and neck squamous cell carcinoma (HNSCC) can 
      experience severe symptom burden and/or difficulty swallowing, leading to 
      problems with treatment adherence/administration. In LUX-Head and Neck 1 (LH&N1; 
      NCT01345682), second-line afatinib improved progression-free survival (PFS) 
      versus methotrexate in patients with recurrent/metastatic HNSCC. We report 
      adherence and safety across pre-specified and additional subgroups potentially 
      linked to afatinib PFS benefit in LH&N1 (p16 status, smoking history), and 
      afatinib adherence, safety and efficacy by administration (oral versus feeding 
      tube; post-hoc analysis). METHODS: Patients were randomized (2:1) to afatinib 
      (40 mg/day) or intravenous methotrexate (40 mg/m(2)/week). RESULTS: Among 320 
      afatinib-treated and 160 methotrexate-treated patients, 83-92% and 76-92% (of 
      patients with data available) across all subgroups took >/=80% of treatment. Across 
      p16 status and smoking history subgroups, the most common treatment-related 
      adverse events (AEs) were diarrhea (70-91%), rash/acne (72-84%), stomatitis 
      (34-73%) with afatinib; and included stomatitis (39-100%), fatigue (22-50%), 
      nausea (19-36%) with methotrexate. Dose reduction decreased AE 
      incidence/severity. Baseline characteristics were generally similar between 
      oral/feeding tube (n = 276/n = 46) groups. 89%/89% (of patients with data 
      available) took >/=80% of assigned afatinib. Median PFS was 2.6 versus 2.7 months 
      (hazard ratio: 0.997; 95% confidence interval: 0.72-1.38). The most common 
      afatinib-related AEs were: rash/acne (74% versus 74%), diarrhea (73% versus 65%), 
      stomatitis (40% versus 30%). CONCLUSION: Subgroup analyses of LH&N1 demonstrate 
      that afatinib has predictable and manageable safety across patient subgroups, 
      with high treatment adherence, and is effective via oral and feeding tube 
      administration.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Haddad, Robert
AU  - Haddad R
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School and Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. 
      Electronic address: robert_haddad@dfci.harvard.edu.
FAU - Guigay, Joel
AU  - Guigay J
AD  - Centre Antoine Lacassagne, FHU OncoAge, Universite Cote d'Azur, Nice, France.
FAU - Keilholz, Ulrich
AU  - Keilholz U
AD  - Medical Department, Charite Comprehensive Cancer Center, Berlin, Germany.
FAU - Clement, Paul M
AU  - Clement PM
AD  - Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
FAU - Fayette, Jerome
AU  - Fayette J
AD  - Medical Oncology, Centre Leon Berard, Lyon, France.
FAU - de Souza Viana, Luciano
AU  - de Souza Viana L
AD  - Department of Medical Oncology, Hospital de Cancer de Barretos, Barretos, Sao 
      Paulo, Brazil.
FAU - Rolland, Frederic
AU  - Rolland F
AD  - Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Nantes, 
      France.
FAU - Cupissol, Didier
AU  - Cupissol D
AD  - Institut du Cancer de Montpellier Val d'Aurelle, Montpellier, France.
FAU - Geoffrois, Lionnel
AU  - Geoffrois L
AD  - Department of Medical Oncology, Institut de Cancerologie de Lorraine, 
      Vandoeuvre-les-Nancy, France.
FAU - Kornek, Gabriela
AU  - Kornek G
AD  - Klinische Abteilung fur Onkologie, Universitatsklinik fur Innere Medizin, Vienna, 
      Austria.
FAU - Licitra, Lisa
AU  - Licitra L
AD  - Department of Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale 
      Tumori, and University of Milan, Milan, Italy.
FAU - Melichar, Bohuslav
AU  - Melichar B
AD  - Department of Oncology, Palacky University Medical School, Olomouc, Czech 
      Republic.
FAU - Ribaldo Nicolau, Ulisses
AU  - Ribaldo Nicolau U
AD  - Department of Oncology, AC Camargo Cancer Center, Sao Paulo, SP, Brazil.
FAU - Rauch, Daniel
AU  - Rauch D
AD  - Swiss Group for Clinical Cancer Research, Bern, Switzerland.
FAU - Zanetta-Devauges, Sylvie
AU  - Zanetta-Devauges S
AD  - Service d'Oncologie Medicale, Centre Georges Francois Leclerc, Dijon Cedex, 
      France.
FAU - Cohen, Ezra E W
AU  - Cohen EEW
AD  - Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
FAU - Machiels, Jean-Pascal
AU  - Machiels JP
AD  - Institut Roi Albert II, Service d'Oncologie Medicale, Cliniques Universitaires 
      Saint-Luc and Institut de Recherche Clinique et Experimentale (Pole MIRO), 
      Universite Catholique de Louvain, Brussels, Belgium.
FAU - Tahara, Makoto
AU  - Tahara M
AD  - Department of Head and Neck Medical Oncology, National Cancer Center Hospital 
      East, Kashiwa, Japan.
FAU - Vermorken, Jan
AU  - Vermorken J
AD  - Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.
FAU - Geng, Yuan
AU  - Geng Y
AD  - Boehringer Ingelheim (China) Investment Co., Ltd., Shanghai, China.
FAU - Zografos, Eleftherios
AU  - Zografos E
AD  - Boehringer Ingelheim Ltd., Berkshire, UK.
FAU - Gauler, Thomas
AU  - Gauler T
AD  - Department of Medicine, West German Cancer Center, University Hospital Essen of 
      the University Duisburg-Essen, Essen, Germany.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190823
PL  - England
TA  - Oral Oncol
JT  - Oral oncology
JID - 9709118
RN  - 0 (Quinazolines)
RN  - 41UD74L59M (Afatinib)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Afatinib/*therapeutic use
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Disease-Free Survival
MH  - ErbB Receptors/metabolism
MH  - Female
MH  - Head and Neck Neoplasms/*drug therapy/metabolism
MH  - Humans
MH  - Male
MH  - Methotrexate/administration & dosage
MH  - Neoplasm Recurrence, Local/*drug therapy/metabolism
MH  - Quinazolines/administration & dosage
MH  - Squamous Cell Carcinoma of Head and Neck/*drug therapy/metabolism
MH  - Treatment Adherence and Compliance
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Adherence
OT  - Afatinib
OT  - Feeding tube
OT  - HNSCC
OT  - Methotrexate
OT  - Recurrent/metastatic
OT  - Safety
EDAT- 2019/08/27 06:00
MHDA- 2020/07/01 06:00
CRDT- 2019/08/27 06:00
PHST- 2019/04/01 00:00 [received]
PHST- 2019/07/26 00:00 [revised]
PHST- 2019/08/03 00:00 [accepted]
PHST- 2019/08/27 06:00 [pubmed]
PHST- 2020/07/01 06:00 [medline]
PHST- 2019/08/27 06:00 [entrez]
AID - S1368-8375(19)30269-6 [pii]
AID - 10.1016/j.oraloncology.2019.08.004 [doi]
PST - ppublish
SO  - Oral Oncol. 2019 Oct;97:82-91. doi: 10.1016/j.oraloncology.2019.08.004. Epub 2019 
      Aug 23.