339TiP - Phase III study of afatinib vs placebo as adjuvant therapy after chemo-radiotherapy (CRT) in primary unresected patients with locoregionally advanc...

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Anticancer Agents
Head and Neck Cancers
Surgical Oncology
Biological Therapy
Radiation Oncology
Presenter Chao Su Hu
Citation Annals of Oncology (2015) 26 (suppl_9): 93-102. 10.1093/annonc/mdv527
Authors C.S. Hu1, A. Chan2, L. Gao3, M.A. Ahn4, E.E.W. Cohen5, M.K. Ang6, Y. Cheng7, Q. Hu8, S.B. Kim9, P. Li10, Y. Sun11, B. Fan12, G. Cheng13, E. Ehrnrooth14, C. Wang15
  • 1Shanghai Cancer Center, Fudan University, 200032 - Shanghai/CN
  • 2Sir Yk Pao Centre For Cancer, The Chinese University of Hong Kong, Hong Kong/CN
  • 3Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Beijing/CN
  • 4Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul/KR
  • 5Department Of Medicine, University of California San Diego Moores Cancer Center, La Jolla/US
  • 6Department Of Medical Oncology, National Cancer Center, Singapore/SG
  • 7Division Of Thoracic Oncology, The Tumor Hospital of Jilin Province, Changchun/CN
  • 8Head And Neck Cancer Center, Zhejiang Cancer Hospital, Hangzhou/CN
  • 9Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 10West China Hospital, Sichuan University, Sichuan/CN
  • 11School Of Oncology, Peking University Cancer Hospital, Beijing/CN
  • 12Medical, Boehringer Ingelheim (China) Investment Co., Ltd, Shanghai/CN
  • 13Biometrics & Data Management, Boehringer Ingelheim (China) Investment Co., Ltd, Shanghai/CN
  • 14Ta Oncology, Boehringer Ingelheim, Danmark A/S/DK
  • 15Department Of Cancer Center, Chang Gung Memorial Hospital - Keelung, Taipei/TW



Following curatively intended CRT, the standard of care for LA HNSCC is observation, and recurrence is common. In a Phase III trial in patients with recurrent and/or metastatic HNSCC progressing on/after platinum-based therapy, afatinib, an irreversible ErbB family blocker, significantly improved progression-free survival and health-related quality of life (HRQoL) vs methotrexate (Machiels, Lancet Oncol 2015). The LUX-H&N2 (global) and LUX-H&N4 (Asia) trials investigate afatinib as adjuvant therapy following CRT in patients with primary unresected LA HNSCC; LUX-H&N4 is described here.

Trial design

Phase III, double-blind, placebo-controlled, randomized study evaluating efficacy and safety of adjuvant afatinib vs placebo after CRT in patients with primary unresected LA HNSCC (NCT02131155). Key eligibility criteria: age ≥18 yrs; ECOG PS of 0 or 1; histologically or cytologically confirmed LA HNSCC; unresected tumor prior to CRT; definitive platinum-based CRT completed ≤24 wks before randomization; no evidence of disease following CRT; unfavorable risk of recurrence (defined as non-oropharynx primary site or oropharynx cancer in heavy smokers [>10 pack yrs]). Exclusion criteria include: base of tongue/tonsil cancer and ≤10 pack yrs smoking history; cancer of nasopharynx, sinuses or salivary glands; prior treatment with EGFR-targeted small molecules/antibodies or investigational agents for HNSCC. Patients are randomized 2:1 to afatinib (40 mg/d orally) or placebo, and will receive continuous treatment for 80 wks or until tumor recurrence/second primary tumor or unacceptable adverse events (AEs). Afatinib must be escalated to 50 mg after ≥4 wks with minimal drug-related 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 primary endpoint is disease-free survival (DFS); secondary endpoints include DFS rate at 2 yrs, overall survival, HRQoL, and safety. Target enrollment is 150 patients; recruitment is ongoing in China, Republic of Korea, Taiwan and Singapore.

Clinical trial identification



A. Chan: advisory board involvement with Merck and Pfizer and research funding from Merck, Eli Lilly, Boehringer Ingelheim and Amgen. M.-J. Ahn: involvement with advisory boards for BMS, ARIAD and Lilly. E. Cohen: advisory board involvement with Merck and Pfizer and honoraria from Eisai and Bayer. B. Fan, G. Cheng, E. Ehrnrooth: employment by Boehringer Ingelheim. All other authors have declared no conflicts of interest.