LUX-Head & Neck 1: 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 methotrexate in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (SqCC) who have progressed after platinum‑based therapy.

Trial CTgov-Identifier: NCT01345682


Histologically or cytologically confirmed SqCC of the oral cavity, oropharynx, hypopharynx or larynx, that was recurrent and/or metastatic and not amenable for salvage surgery or radiotherapy
Documented progressive disease based on investigator assessment according to Response Evaluation Criteria in Solid Tumors
Eastern Cooperative Oncology Group performance status 0‑1

N = 483

Randomisation 2:1

  • Afatinib 40 mg
    Oral once daily

  • Methotrexate 40 mg/m2
    Intravenous once weekly


Primary Outcome Measures:
Progression free survival (PFS), assessed by an independent central review

Secondary Outcome Measures:
Overall survival (OS)
Objective response (OR)
Disease control rate (DCR)
Tumour shrinkage
Health‑related quality of life


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 months vs 1.7 months with chemotherapy. This translated into a 20% reduction in risk of disease progression.

PFS figure1


Median OS was longer in patients treated with afatinib compared with patients on methotrexate, however the difference between the two arms was not statistically significant.

OS figure2


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

DCR figure3


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

Adverse events (AEs) 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.


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


Machiels J-P, Haddad RI, Fayette J, et al. LUX-Head & Neck 1: Afatinib versus methotrexate as second-line treatment for patients (pts) with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy. Lancet Oncol 2015;16(5):583–594.
(Accessed: May 2016).