Phase III study of afatinib vs placebo as adjuvant therapy after chemo-radiotherapy (CRT) in primary unresected patients with locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) in Asia: LUX-Head & Neck 4 (LUX-H&N4)

Background

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

NCT02131155

Disclosure

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.