Merck KGaA’s monoclonal antibody cancer drug Erbitux (cetuximab) has broken new ground in head and neck cancer this week with the release of Phase III data on first-line use in patients with severe disease.

Late-breaking results of EXTREME, a European multi-centre randomised study presented in Chicago at the annual meeting of the American Society of Clinical Oncology, show first-line Erbitux added to platinum-based chemotherapy significantly extends survival in patients with stage III/IV recurrent or metastatic squamous cell cancer of head and neck (R/MSCCHN).

Erbitux, which blocks tumour growth by targeting the epidermal growth factor receptor (EGFR) on the surface of solid tumours, is already approved for use in R/MSCCHN in the USA where it is marketed by Bristol-Myers Squibb and Imclone. In Europe it is currently approved only for treatment of locally advanced SCCHN in combination with radiation therapy. This indication is supported by a much-cited prior phase III study of 424 patients which showed Erbitux and radiotherapy compared to radiotherapy alone significantly extended survival by almost 20 months in locally advanced disease. However, in the UK, even this data has not been sufficient to convince NICE of its cost effectiveness.

Oncologist Professor Jan Vermorken of University of Antwerp, Belgium, who led the 442-patient EXTREME study, said the results constituted ‘a breakthrough’ in the category of very severe head and neck cancer patients with recurrent or metastatic disease where no treatment has previously managed to extend survival beyond seven months. In EXTREME, patients randomised to receive Erbitux in addition to cisplatin or carboplatin and 5-FU had a median survival of 10.1 months compared to 7.4 months for chemotherapy alone.

The 2.7 months extra survival represent a greater than 20% reduced risk of death (hazard ratio 0.797 p<0.03). Overall survival at one year was 39% for patients who received Erbitux versus 31% for those who did not. The survival benefit was achieved without adding to the burden of side effects experienced with chemotherapy, he stressed. The only notable additional side effect was the presence of skin rash associated with response to Erbitux.

In the study patients randomised to Erbitux received the standard weekly dose schedule in addition to a maximum of six cycles of chemotherapy. They could then continue on Erbitux alone until their disease progressed. The survival analysis was conducted as planned after 340 events had occurred.

Professor Vermorken commented: “This is the first systemic treatment to show a survival benefit over platinum-based chemotherapy in this patient population in 25 years.” These patients traditionally have a very poor outcome and the data are likely to have a substantial impact on clinical practice, he predicted. SCCHN is the sixth most common cancer with more than half a million new cases worldwide; of these 30,000 are in the US and around 68,000 in Europe.

Merck KGaA spokesman Wolfgang Wein said: “EXTREME’s favourable results should help create a solid basis for a future license application in Europe. When all the data is available, Merck KGaA will submit a variation application to the EMEA.” By Olwen Glynn Owen