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LUX-Head & Neck 1 clinical trial

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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 (SqCC) who have progressed after platinum-based therapy.

Trial NCT01345682


SqCC 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 40 mg Oral once daily
Methotrexate 40 mg/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 rash/acne (Grade 3/4=10%) and diarrhoea (Grade 3/4=9%) with afatinib and stomatitis (Grade 3/4=8%) and neutropenia (11%) with methotrexate.

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: July 2017).

*Afatinib is approved in more than 70 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. Afatinib is being investigated in urothelial carcinoma (UC) and head and neck squamous cell carcinoma (HNSCC) and is not approved for these uses. The efficacy and safety of afatinib in UC and HNSCC have not been established.