Patients with incurable squamous-cell carcinoma of the head and neck (SCCHN) whose chemotherapy is no longer working, who are given zalutumumab, survive significantly longer without the disease progressing than patients receiving best supportive care (BSC)*.
These findings from the first randomised trial of zalutumumab in patients with SCCHN, published Online First in The Lancet Oncology, support zalutumumab therapy as a treatment option for these patients. However, the findings also show that despite a nearly 30% improvement in overall survival (OS) in patients taking zalutumumab, this increase was not significantly different to patients given BSC.
For patients with recurrent or metastatic SCCHN whose platinum-based chemotherapy is no longer working the prognosis is poor and they are considered incurable. Currently, there are no treatment options available to increase survival in this group of patients. Most head and neck cancers express the epidermal growth factor receptor (EGFR) which is linked to poor outcome. Zalutumumab is a monoclonal antibody that targets EGFR and has been shown to inhibit tumour growth in preclinical studies.
Jean-Pascal Machiels from the Cliniques Universitaires Saint Luc, Brussels, Belgium and colleagues did a phase 3 trial to assess the effect of zalutumumab on overall and progression-free survival (PFS) in patients with recurrent or metastatic SCCHN after failure of chemotherapy. 286 patients were recruited from 67 centres across Europe, Brazil, and Canada and randomly assigned to zalutumumab plus BSC (191 patients) or BSC alone (95 patients). OS and PFS were determined by clinical examination and CT or MRI.
Zalutumumab treatment was associated with significantly better PFS, but did not significantly increase OS (median OS: 6.7 vs 5.2 months). Importantly, a long-term PFS benefit was achieved by a group of patients shown by a PFS rate at 6 months of 20% in the zalutumumab group compared with 7.3% in the BSC group.
Interestingly, PFS and OS seemed to be longer in patients with high EGFR expression compared with low EGFR expression, a finding not reported in previous studies that should be investigated in further trials.
Zalutumumab treatment was generally well tolerated. However, more grade 3 or 4 adverse events were reported in the zalutumumab group and included rash (21% vs 0), anaemia (6% vs 5%), and pneumonia (5% vs 2%). Grade 3 and 4 infections were also more frequent in patients treated with zalutumumab (15%) than with BSC alone (9%). The most common serious adverse events were tumour haemorrhage (15% of patients taking zalutumumab vs 14% BSC alone), pneumonia (7% vs 3%), and difficulty swallowing (6% vs 2%). The authors say: "Our study supports the use of an anti-EGFR monoclonal antibody after platinum failure in patients with squamous-cell carcinoma of the head and neck."
Professor Jean-Pascal Machiels, Cliniques Universitaires Saint Luc, Brussels, Belgium. Via Communications Department T) +32 276 411 99 E) jean-pascal.machiels@uclouvain.be http://www.centreducancer.be
Notes to Editors: *Best supportive care (BSC) involves treatment to control cancer symptoms and improve quality of life.
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Journal
The Lancet Oncology