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Cetuximab continues to increase survival in patients with head and neck cancer for up to 5 years

7 Nov 2009

Adding cetuximab to radiation therapy prolongs survival in patients with locally advanced head and neck cancer compared with radiotherapy alone, and this improvement persists for up to 5 years. As such, this combined treatment should be considered as a standard option for patients with advanced head and neck cancer, concludes an article published in The Lancet Oncology.

Standard treatment for head and neck cancer is radiotherapy in combination with surgery. The use of chemoradiotherapy has been shown to improve survival and has become a popular treatment, but is not ideal because of its associated side-effects and increased toxicity.

Most head and neck cancers express the epidermal growth factor receptor (EGFR), which is linked to poor clinical outcome and decreased response to radiotherapy. However, cetuximab is a monoclonal antibody that targets EGFR, and has been shown to enhance the effect of radiotherapy and inhibit tumour growth in preclinical studies.

In 1999, a trial commenced to examine the effect of adding cetuximab to radiotherapy in patients with locally advanced head and neck cancers of the oropharynx, hypopharynx, and larynx. In total, 424 patients were randomly assigned to 6–7 weeks of radiotherapy alone (213) or radiotherapy and cetuximab (211). The primary results of the trial showed that patients treated with cetuximab had a 13% improvement in absolute disease control and 10% improvement in absolute survival at 3 years without increased side-effects, compared with patients given radiotherapy alone.

 

In this study, James Bonner and colleagues report the long-term 5-year outcomes of patients involved in the original trial.

Overall, findings showed an improvement in absolute survival of about 9% in patients given cetuximab compared with those given radiotherapy alone (36.4% vs 45.6%) at 5 years.

Interestingly, the authors found that patients treated with cetuximab who developed a prominent cetuximab-induced acne-like rash showed significantly improved overall survival compared with patients given cetuximab who developed a mild or no rash (more than 68.8 months vs 25.6 months). They suggest that the rash could be a biomarker for an immunological response that is associated with a favourable outcome.

Further analyses also showed that various patient and tumour factors (such as having an oropharynx tumour, being male, and aged less than 65 years) were associated with an improved benefit from combined treatment with cetuximab and radiotherapy compared with radiotherapy alone.

The authors conclude: “Future studies will be designed to help provide a pathway to individualised patient treatments. The analysis of molecular markers…will help refine our ability to select the patients who will benefit from the various systemic treatments to radiotherapy.”