An article published Online First in The Lancet Oncology reports that adding cetuximab to radiation therapy prolongs survival in patients with locally advanced head and neck cancer compared with radiotherapy alone. This improvement persists for up to five years. As a result, this combined treatment should be considered as a standard option for patients with advanced head and neck cancer.
Radiotherapy in combination with surgery is standard treatment for head and neck cancer. The use of chemo-radiotherapy has been shown to improve survival and has become a popular treatment. However, it is not ideal because of it is linked to side-effects and increased toxicity.
Generally, head and neck cancers express the epidermal growth factor receptor (EGFR). It is linked to poor clinical outcome and decreased response to radiotherapy. However, cetuximab is a monoclonal antibody that targets EGFR. It has proven to enhance the effect of radiotherapy and inhibit tumour growth in preclinical studies.
A trial began in 1999 to study the effect of adding cetuximab to radiotherapy in patients with locally advanced head and neck cancers of the oropharynx, hypopharynx, and larynx. Overall, 424 patients were randomly assigned to 6 to 7 weeks of radiotherapy alone (213 patients) or radiotherapy and cetuximab (211 patients). The principal results of the trial indicated that patients treated with cetuximab had a 13 percent improvement in absolute disease control and 10 percent improvement in absolute survival at three years without increased side-effects, compared with patients given radiotherapy alone.
James Bonner and colleagues report in this study the long-term five-year outcomes of patients involved in the original trial.
In general, findings indicated there was an improvement in absolute survival of about 9 percent in patients given cetuximab compared with those given radiotherapy alone (36.4 percent compared to 45.6 percent) at five years.
According to the results, an interesting fact was that patients treated with cetuximab who developed a prominent cetuximab-induced acne-like rash showed a much improved overall survival compared with patients given cetuximab who developed a mild or no rash (more than 68.8 months compared to 25.6 months). The authors suggest that the rash could be a biomarker for an immunological response that is associated with a positive outcome.
Also, additional analyses indicated that several patient and tumour factors such as having an oropharynx tumour, being male and aged less than 65 years, were associated with a superior benefit from combined treatment with cetuximab and radiotherapy compared with radiotherapy alone.
The authors write in conclusion: “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.”
“Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival”
James A Bonner, Paul M Harari, Jordi Giralt, Roger B Cohen, Christopher U Jones, Ranjan K Sur, David Raben, Jose Baselga, Sharon A Spencer, Junming Zhu, Hagop Youssoufian, Eric K Rowinsky, K Kian Ang
DOI: 10.1016/S1470-2045(09)70311-0
Written by Stephanie Brunner (B.A.)