Data presented at the 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology show that patients with non-small cell lung cancer (NSCLC) who were given Erbitux (cetuximab) in addition to a standard 1st-line platinum-based chemotherapy lived significantly longer than those who received chemotherapy alone. This effect was more pronounced in patients treated with Erbitux who developed early acne-like rash, resulting in median overall survival of 15 months.

In the overall population of FLEX the addition of Erbitux to chemotherapy prolongs median overall survival from 10.1 to 11.3 months (Hazard Ratio HR=0.87, p=0.04). The new analysis demonstrated that overall survival for patients receiving Erbitux, who experienced any grade of rash (acne-like rash) within three weeks of treatment initiation, was 15.0 months compared to 8.8 months in those patients who developed no rash (HR=0.63, p<0.001).1 Therefore, development of such a skin rash is associated with a better outcome for patients treated with Erbitux in combination with chemotherapy. It appears to be an important indicator for longer survival.

"As physicians, we have been waiting for the best part of a decade for a novel treatment that would yield a significant increase in the key endpoint in NSCLC - overall survival - and now FLEX will give us a new option, Erbitux, to use with our patients," said Dr Ulrich Gatzemeier of the Hospital Grosshansdorf, Germany, one of the lead FLEX trial investigators. "In addition, patients who develop the early skin rash can take comfort from the fact that it appears to be a clear signal that the drug is working."

The FLEX trial was a multinational, randomized, Phase III study which involved a total of 1,125 patients with stage IIIB and IV NSCLC, representing all histological subtypes and ECOG performance status 0-2. Overall patients randomized to the Erbitux treatment arm survived for additional 1.2 months, compared to those receiving chemotherapy alone (11.3 vs. 10.1 months; Hazard Ratio HR=0.87, p=0.04). Response rate and time to treatment failure were also significantly improved (p=0.01 and 0.02 respectively). Erbitux was well tolerated in this trial, with expected and manageable side effects including the development of skin rash, which was only observed as grade 1-3. The FLEX trial forms the basis for the submission to the European Medicines Agency (EMEA) in September 2008.

In a pre-planned analysis the relation of early-onset skin rash (i.e. within three weeks of treatment initiation) and efficacy of Erbitux was evaluated. The new data demonstrate a particularly high median overall survival of 15.0 months (95% CI 12.8-16.4 months) in those FLEX patients who showed any grade of rash (grade 1-3; 56%; n=290), whereas overall survival was 8.8 months (95% CI 7.6-11.1 months) in patients who developed no rash (n=228). This difference was reflected in a Hazard Ratio of 0.63 (95% CI 0.52-0.77, p<0.001). Patients' characteristics in both groups were similar.

"A 15 month survival in patients with early skin rash achieved in a clinical trial that included an overall population with 94% being stage IV and 17% with an ECOG performance status 2 marks an outstanding signal of efficacy and opens the door to new treatment strategies in NSCLC," said Dr Wolfgang Wein, Executive Vice President, Oncology, Merck Serono, a division of Merck KGaA.

Erbitux is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumour cells and the spread of tumours to new sites. It is also believed to inhibit the ability of tumour cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumours, which appears to lead to an overall suppression of tumour growth.

The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in 75 countries. It has been approved for the treatment of colorectal cancer in 74 countries.

Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs.