The tyrosine kinase inhibitor (TKI) afatinib significantly improved progression-free survival compared with methotrexate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy, according to the results of a phase III trial. These results were presented at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain.

The Lux-Head & Neck 1 trial showed that patients who received treatment with 40 mg/day oral afatinib had a 20% reduction in risk of disease progression or death compared with patients who received methotrexate, with a median progression-free survival of 2.6 months.

“The improvement in progression-free survival was associated with a significant delayed worsening of symptoms (such as pain, swallowing, and global health status) versus chemotherapy. Patients treated with afatinib had less pain over time than patients treated with methotrexate. “These are important outcomes for patients with these conditions,” noted study author Jean-Pascal Machiels, MD, PhD, a medical oncologist at Institut Roi Albert II, Cliniques Universitaires St. Luc, in Brussels, Belgium.

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Recurrent or metastatic squamous cell carcinoma of the head and neck often has a poor outcome, Machiels explained. “This is a poor prognosis population and a disease that does not get enough attention from the scientific community, because this group of patients often has severe co-morbidities and social problems such as alcoholism and tobacco use.”

“Frequently these patients have a relapse in the head and neck area. This location is responsible for many symptoms that are difficult to palliate: pain, breath disorder, and swallowing difficulties.”

Afatinib is a compound that irreversibly blocks the ErbB family of cell surface receptors, which includes epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), HER3, and HER4. Approximately 90% of squamous cell carcinomas of the head and neck overexpress EGFR.

In the latest trial, researchers aimed to see if inhibiting multiple ErbB receptors simultaneously would improve the clinical efficacy of EGFR-targeted therapy. They studied 483 patients with recurrent or metastatic head and neck squamous cell carcinoma whose cancer had progressed despite treatment with platinum-based therapy. Overall, 322 patients received 40 mg/day oral afatinib and 161 were given 40 mg/m2/week intravenous methotrexate.

The study met its primary end point and afatinib significantly improved progression-free survival versus methotrexate, Machiels said. The trial was not able to demonstrate that afatinib improves survival. “Afatinib improved progression-free survival and delayed worsening of symptoms, and it is the first tyrosine kinase inhibitor to demonstrate a significant benefit in this disease.”

The toxicity profile was acceptable and manageable with afatinib: the most frequent grade 3/4 drug-related adverse events were rash/acne (9.7%) and diarrhea (9.4%). Less treatment-related dose reductions, discontinuations, and fatal events were seen with afatinib.

“We are pleased with the results because we showed a benefit, although modest, in a very well-designed controlled trial,” Machiels said. “The difference of this trial compared to the others performed in the same setting is that it was a homogenous population. It sets a kind of baseline design that could be used to design further trials.”