340TiP - Phase III study of afatinib vs methotrexate (MTX) for second-line recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) p...

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Anticancer agents
Head and Neck Cancers
Biological therapy
Presenter Ping Zhang Tang
Citation Annals of Oncology (2015) 26 (suppl_9): 93-102. 10.1093/annonc/mdv527
Authors P.Z. Tang1, M.A. Ahn2, Q. Zhang3, A. Chan4, S.B. Kim5, C. Wang6, X. He7, W. Guo8, J.H. Kang9, A. Dechaphunkul10, P. Li11, A. Kandil12, E.E.W. Cohen13, G. Hu14, Y. Geng15, E. Ehrnrooth16, Y. Guo17
  • 1Cancer Institute & Hospital, Chinese Academy of Medical Sciences, 100021 - Beijing/CN
  • 2Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul/KR
  • 3Department Of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin/CN
  • 4Sir Yk Pao Centre For Cancer, The Chinese University of Hong Kong, Hong Kong/CN
  • 5Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 6Department Of Cancer Center, Chang Gung Memorial Hospital- Keelung, Taipei/TW
  • 7Cancer Hospital, Chinese Academy of Medical Science, Beijing/CN
  • 8Department Of Oral And Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai/CN
  • 9The Catholic University Of Korea, Seoul St. Mary's Hospital, Seoul/KR
  • 10Department Of Internal Medicine, Prince of Songkla University, Songkhla/TH
  • 11West China Hospital, Sichuan University, Chengdu/CN
  • 12Faculty Of Medicine, Alexandria University School of Medicine, Alexandria/EG
  • 13Department Of Medicine, University of California San Diego Moores Cancer Center, La Jolla/US
  • 14Clinical Operations, Boehringer Ingelheim (China) Investment Co., Shanghai/CN
  • 15Biometrics & Data Management, Boehringer Ingelheim (China) Investment Co., Shanghai/CN
  • 16Ta Oncology, Boehringer Ingelheim, Danmark A/S/DK
  • 17Shanghai Cancer Center, Fudan University, Shanghai/CN



HNSCC patients who progress after first-line platinum-based CT for R/M disease have few treatment options. In the Phase III LUX-H&N1 trial, afatinib, an irreversible ErbB family blocker, significantly improved progression-free survival (PFS) and health-related quality of life (HRQoL) compared with MTX in this patient population (Machiels et al, Lancet Oncol 2015). The LUX-H&N3 trial, sharing a similar study design, evaluates afatinib vs MTX in the same treatment setting in patients in Asia/Middle East/North Africa.

Trial design

LUX-H&N3 is a Phase III, open-label, randomized trial evaluating efficacy and safety of afatinib vs MTX in R/M HNSCC patients progressing on/after first-line platinum-based CT (NCT01856478). Key eligibility criteria: age ≥18 years; ECOG PS 0 or 1; histologically or cytologically confirmed R/M HNSCC not amenable for salvage surgery or radiotherapy; documented progressive disease (PD) after ≥2 cycles of cisplatin/carboplatin for R/M disease (>1 systemic therapy not allowed). Prior treatment with EGFR-targeted antibody therapy but not EGFR-targeted small molecules is allowed. Patients are randomized 2:1 to afatinib (40 mg/day orally) or MTX (40 mg/m2 IV weekly), stratified by ECOG PS (0/1) and prior EGFR-targeted antibody therapy in the R/M setting (Yes/No). The initial afatinib dose must be escalated to 50 mg after ≥4 weeks with minimal drug-related adverse events (AEs), or reduced by 10 mg decrements to a minimum of 20 mg in case of drug-related grade ≥3 or selected grade 1/2 AEs. The MTX dose can be escalated to 50 mg/m2, or reduced by 10 mg/m2 decrements to a minimum of 20 mg/m2 in case of drug-related grade ≥2 or selected grade >1 AEs. Treatment will continue until PD or intolerable AEs. Treatment may continue beyond PD in case of clinical benefit as judged by the investigator. The primary endpoint is PFS; secondary endpoints include overall survival, objective response, HRQoL, and safety. Target enrollment is 300 patients; recruitment is ongoing.

Clinical trial identification



M.-J. Ahn: involvement with an advisory board for BMS, ARIAD and Lilly.

A. Chan: advisory board involvement with Merck and Pfizer and research funding from Merck, Eli Lilly, Boehringer Ingelheim and Amgen. J.H. Kang: advisory board involvement with Boehringer Ingelheim, Eli Lilly, Pfizer and ONO Pharmaceutical Co.; corporate-sponsored research for Eli Lilly; and honoraria from Pfizer, Novartis and Boehringer Ingelheim. E. Cohen: involvement with an advisory board for Merck and Pfizer and honoraria from Eisai and Bayer. G.-Q. Hu, Y. Geng, E. Ehrnrooth: employment with Boehringer Ingelheim.

All other authors have declared no conflicts of interest.