LBA29_PR - Afatinib versus methotrexate (MTX) as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcino...

Date 27 September 2014
Event ESMO 2014
Session Head and neck cancer
Topics Anticancer Agents
Head and Neck Cancers
Biological Therapy
Presenter Jean-Pascal Machiels
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors J. Machiels1, R.I. Haddad2, J. Fayette3, L. Licitra4, M. Tahara5, J. Vermorken6, P.M. Clement7, T.C. Gauler8, D. Cupissol9, J.J. Grau10, J. Guigay11, F. Caponigro12, G. De Castro Jr13, L. De Souza Viana14, U. Keilholz15, J.M. Del Campo16, X.J. Cong17, L. Svensson18, E. Ehrnrooth18, E.E.W. Cohen19
  • 1Oncology, Cancer Center, Service d’Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, 1200 - Brussels/BE
  • 2Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School, Boston/US
  • 3Medical Oncology, Léon Bérard Center, University of Lyon, LYON/FR
  • 4Medical Oncology, Istituto Nazionale Tumori, Milan/IT
  • 5Head And Neck Medical Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 6Medical Oncology, Antwerp University Hospital, Edegem/BE
  • 7Medical Oncology, KU Leuven, Leuven/BE
  • 8Medical Oncology, West German Cancer Center, University Hospital Essen, Essen/DE
  • 9Medical Oncology, Institut du Cancer de Montpellier Val d’Aurelle, Montpellier/FR
  • 10Oncology, Hospital Clínic de Barcelona, Barcelona/ES
  • 11Medical Oncology, 11 Gustave Roussy, Villejuif, at present Centre Antoine Lacassagne, Nice/FR
  • 12Head And Neck – Medical Oncology, National Tumor Institute of Naples, Naples/IT
  • 13Clinical Oncology, Instituto do Câncer do Estado de São Paulo, São Paulo/BR
  • 14Medical Oncology, Hospital de Câncer de Barretos, São Paulo/BR
  • 15Medical Oncology, Charité Comprehensive Cancer Center, Berlin/DE
  • 16Medical Oncology, Hospital Universitario Vall D’Hebron, Barcelona/ES
  • 17Medical Oncology, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield/US
  • 18Medical, Boehringer Ingelheim, Danmark A/S/DK
  • 19Medicine, University of California San Diego Moores Cancer Center, La Jolla/US



Patients with R/M HNSCC who progress after first-line platinum-based therapy have a dismal prognosis and no well-defined treatment. Afatinib, an irreversible ErbB family blocker, showed anti-tumor activity in a phase II trial in this setting.


In this phase III trial, patients with R/M HNSCC after progression on/after platinum-based therapy were randomised 2:1 to 40 mg/day oral afatinib (n = 322) or 40 mg/m2/week intravenous MTX (n = 161), stratified by ECOG performance status (0/1) and prior use of anti-EGFR antibody therapy (Yes/No) in the R/M setting. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), patient-reported outcomes (PROs) and safety.


Afatinib significantly improved the primary endpoint of PFS vs MTX (median 2.6 vs 1.7 months; HR = 0.80 [95% CI 0.65–0.98; p = 0.03]), but did not significantly improve OS vs MTX (median 6.8 vs 6.2 months; HR = 0.94 [0.75–1.18]). Disease control rate was higher with afatinib vs MTX (49.1% vs 38.5%; p = 0.04); ORR was 10.2% vs 5.6% (p = 0.10). Tumour shrinkage from baseline was observed in 34.8% of afatinib-treated patients compared to 22.4% of MTX-treated patients. Afatinib delayed deterioration of global health status, pain and swallowing vs MTX (all p ≤ 0.03) and provided improvement in pain (p = 0.03). The most frequent grade 3/4 drug-related adverse events were rash/acne (9.7%) and diarrhoea (9.4%) with afatinib, and leukopenia (15.6%) and stomatitis (8.1%) with MTX. Fewer treatment-related dose reductions, discontinuations and fatal events were seen with afatinib. Additional optional biomarker analyses, including p16 status, will be presented.


In this phase III trial, second-line afatinib significantly improved the primary endpoint of PFS and delayed deterioration of PROs vs MTX, with a manageable safety profile, in patients with R/M HNSCC after failure of platinum-based therapy. Machiels JPH, Haddad RI and Fayette J contributed equally to this work.


J-P. Machiels: Advisory boards for Boehringer Ingelheim, Novartis; R.I. Haddad: Advisory boards for Celgene, Bayer Corporate sponsored research for Boehringer Ingelheim; L.F. Licitra: Advisory boards for Eisai, Bristol-Myers Squibb, GlaxoSmithKline, Merk-Serono, Amgen, Boehringer Ingelheim, Debiopharm, VentiRX, Sobi, F. Hoffmann-La Roche, Celgene; M. Tahara: Advisory boards for Eisai, Boehringer Ingelheim, Otsuka Pharmaceutical Corporate sponsored research for Eisai, Boehringer Ingelheim Other substantive relationships with Merck Serono, Bristol-Myers Squibb; J.B. Vermorken: Advisory boards for Merck Serono, Genentech Other substantive relationships with Steering CIE LUX-H&N 2 trial; P.M. Clement: Advisory boards for Merck Serono, Leo Pharma, Grünenthal Corporate sponsored research for Merck Sharp & Dohme, Grünenthal; T. Gauler: Stock ownership with Bayer AG Advisory boards for Boehringer Ingelheim (BI), Merck Serono, Novartis Corporate sponsored research for BI (ITS), Merck Serono (ITS) Other substantive relationships with BI, Merck Serono; G. De Castro Jr: Advisory boards for Boehringer Ingelheim, Bayer, F. Hoffmann-La Roche, Novartis; X.J. Cong, L. Svensson and E. Ehrnrooth: Other substantive relationships with Employee, Boehringer Ingelheim. All other authors have declared no conflicts of interest.