Afatinib Improves Progression-Free Survival vs Methotrexate in Platinum-Treated Recurrent or Metastatic Head and Neck Cancer


Key Points

  • Afatinib improved progression-free survival vs methotrexate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing after first-line platinum treatment.
  • Some subgroups appeared to derive greater benefit from afatinib treatment.

In the phase III LUX-Head & Neck 1 trial reported in The Lancet Oncology, Machiels et al found that afatinib (Gilotrif) improved progression-free survival vs methotrexate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing after first-line platinum treatment.

Study Details

In this open-label trial, 483 patients from 19 countries were randomly assigned 2:1 between January 2012 and December 2013 to afatinib at 40 mg/d (n = 322) or methotrexate at 40mg/m2 weekly (n = 161). Patients could not have received more than one prior systemic treatment for recurrent/metastatic disease; previous treatment with EGFR-targeted antibody therapy but not EGFR-targeted tyrosine kinase inhibitors was permitted. The primary endpoint was progression-free survival on independent review in the intention-to-treat population.

Patients had a median age of 59 to 60 years (26%–28% aged ≥ 65 years) and most were male (85%), had Eastern Cooperative Oncology Group performance status of 1 (72%–74%), and had received prior anti-EGFR antibody treatment for recurrent/metastatic disease (59%–61%). Locoregional disease only was present in 33% to 38%, 11% to 14% had distant metastasis only, and 48% to 51% had both. The lung was the most common metastatic site (47%–48%).

Efficacy Outcomes

After a median follow-up of 6.7 months, median progression-free survival was 2.6 months (95% confidence interval [CI] = 2.0–2.7 months) in the afatinib group vs 1.7 months (95% CI = 1.5–2.4 months) in the methotrexate group (hazard ratio [HR] = 0.80, P = .030). Median overall survival was 6.8 months (95% CI = 6.1–7.7 months) vs 6.0 months (5.2–7.8 months; HR = 0.96, P = .70). Objective response rates (all partial responses) were 10% vs 6% and disease control rates were 49% vs 39%.

In stratification and subgroup analyses, there appeared to be greater progression-free survival benefit with afatinib in patients who had not previously received anti-EGFR antibody treatment for recurrent/metastatic disease, men, patients with larynx cancer, patients with locally recurrent vs metastatic disease, and smokers with ≥ 10 pack-years history.

Adverse Events

The most common grade 3 or 4 drug-related adverse events were rash/acne (10% in afatinib group vs 0% in methotrexate group), diarrhea (9% vs 2%), stomatitis (6% vs 8%), fatigue (6% vs3%), and neutropenia (< 1% vs 7%). Treatment-related serious adverse events occurred in 14% vs 11%. Treatment-related adverse events led to discontinuation of study treatment in 7% vs 16%. Death considered related to study treatment occurred in two afatinib patients (septic shock and aspiration pneumonia) and five methotrexate patients (septic shock, sepsis, aspiration pneumonia, general health deterioration, renal failure with pancytopenia).

The investigators concluded: “Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in [head and neck squamous cell carcinoma].”

Jean-Pascal H. Machiels, MD, of Université Catholique de Louvain, Brussels, is the  corresponding author for The Lancet Oncology article.

The study was funded by Boehringer Ingelheim. For full disclosures of the study authors, visit

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