Afatinib Improves Progression-Free Cancer Survival

afatinib (Source: trc-canada.com)
Afatinib, a tyrosine kinase inhibitor, significantly improved progression-free survival compared to methotrexate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy, the results of a phase III trial presented at the ESMO 2014 Congress in Madrid show.

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 progression or death compared to patients who received methotrexate, with a median progression-free survival of 2.6 months. Frequently these patients have a relapse in the head and neck area. This location is responsible of 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. Around 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 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.
 
Future studies should focus on understanding which patient groups derive a clinically meaningful benefit from afatinib, the researchers says. They hope to provide further molecular insights and hypotheses to identify patients who benefit.
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