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LUX-Head & Neck 1 clinical trial

A Phase III Trial of Afatinib vs Methotrexate for the Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma After Platinum-Based Chemotherapy

A randomised, open-label, Phase III study to evaluate the efficacy and safety of oral afatinib* vs intravenous (IV) methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed after platinum-based therapy.

Trial NCT01345682


Squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, that was recurrent and/or metastatic and not amenable for salvage surgery or radiotherapy

Progressive disease after first-line cisplatin or carboplatin (≥2 cycles) for recurrent and/or metastatic disease

No prior treatment with epidermal growth factor receptor (EGFR) inhibitors

Eastern Cooperative Oncology Group performance status of 0–1



Randomisation 2:1

Afatinib 40mg Oral once daily
Methotrexate 40mg/m² IV once weekly


Primary outcome measure:

  • Progression free survival (PFS), assessed by  independent central review


Key secondary outcome measure:

  • Overall survival (OS)


Secondary outcome measures:

  • Objective response (OR)
  • Disease control rate (DCR)
  • Tumour shrinkage
  • Health-related quality of life (HRQoL)



LUX-Head & Neck 1 met its primary endpoint of PFS and showed that patients taking afatinib after failure of previous platinum-based chemotherapy experienced a significant delay in tumour growth of 2.6 vs 1.7 months with methotrexate (MTX). This translated into a 20% reduction in risk of disease progression.

Hazard ratio = 0.80 95% CI = 0.65–0.98
LUX-Head & Neck 1: figure for PFS with afatinib vs methotrexate


OS was not significantly different between afatinib and methotrexate.

LUX-Head & Neck 1: figure for overall survival with afatinib vs methotrexate


DCR was achieved in 49.1% of patients on afatinib vs 38.5% of patients on methotrexate.

LUX-Head & Neck 1: figure for DCR with afatinib vs methotrexate


Compared with methotrexate, afatinib was associated with delayed time to deterioration of global health status (3.3 vs 2.7 months, p=0.027), pain (3.0 vs 2.3 months, p=0.022) and swallowing (3.8 vs 2.1 months, p=0.004).


Adverse events (AEs) of Grade ≥3 occurred in 67% of patients in the afatinib group compared with 63% in the methotrexate group. The most frequent AEs were:

  • For afatinib:
    • Rash/acne (Grade 3/4=10%)
    • Diarrhoea (Grade 3/4=9%)
  • For methotrexate:
    • Stomatitis (Grade 3/4=8%)
    • Neutropenia (Grade 3/4=7%)

Subgroup analysis according to age:

Analysis according to the pre-specified subgroups of patients aged ≥65 years and <65 years showed similar results for efficacy, safety and HRQoL. Advancing age did not adversely affect outcomes following afatinib treatment.

Subgroup analysis according to characteristics linked to HPV negativity:

Post-hoc analyses found that subgroups of patients that had baseline characteristics potentially linked to human papillomavirus (HPV) negativity (i.e. p16-negative disease, primary disease in the larynx, and smoking history ≥10 pack-years) exhibited a greater benefit in PFS with afatinib than with methotrexate.


Afatinib was associated with significant improvements in PFS and had a manageable safety profile.


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Machiels J-P, et al. Lancet Oncol 2015;16(5):583–594.


Clement PM, et al. Ann Oncol 2016;27:1585–1593.

3 (Accessed: June 2019).

*Afatinib is approved in more than 80 markets including the EU, Japan, Taiwan, and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list please see here. Registration conditions differ internationally; please refer to locally approved prescribing information. The efficacy and safety of afatinib in HNSCC has not been established.

Page last updated: September 2017