ImClone Systems Incorporated and Bristol-Myers Squibb Company announced five-year overall survival data from the pivotal phase-3 study examining Erbitux (cetuximab) combined with radiation in patients with locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN). The results were presented at the American Society for Therapeutic Radiology and Oncology (ASTRO) Annual Meeting in Boston.
Analysis of these five-year data demonstrate that the addition of Erbitux to radiation therapy resulted in a significant increase in median overall survival for patients with SCCHN, when compared to radiation therapy alone. The overall survival rate at five years was 45 per cent vs. 36 percent, respectively (p=0.018); survival rate at three years was 55 per cent vs. 45 percent (p=0.05), respectively. These data are consistent with results in the current head and neck labelling for Erbitux, which include the median overall survival rate.
"Erbitux in combination with radiation demonstrated a statistically significant improvement in overall survival versus radiation alone at five years," said James Bonner, University of Alabama, principal investigator for the study. "These results are important for both physicians and patients because this is a difficult type of cancer to treat."
The international, randomized study (IMCL-9815), conducted by ImClone and its partner Merck KGaA, Darmstadt, Germany, enrolled 424 previously untreated patients with locally or regionally advanced squamous cell carcinoma of the oropharynx (area of the throat at the back of the mouth), larynx (voice box) or hypopharynx (cavity at the back of the mouth that opens into the esophagus) that has spread through the head and neck region. Patients were randomly assigned to receive Erbitux plus radiation (n=211) or radiation alone (n=213) for six to seven weeks. Erbitux was dosed weekly, starting one week before radiation and for the duration of radiation therapy. The median number of Erbitux doses administered in the clinical study was eight (1-11 infusions). As part of this pre-specified analysis, patients were evaluated during semi-annual follow-up exams during years three through five.
"These updated five-year overall survival data further support our belief in Erbitux as the first biologic approved to treat head and neck cancer in more than 30 years, and are part of a comprehensive clinical development program designed to fully understand the potential uses of Erbitux for cancer patients," said Maurizio Voi, executive director, Oncology Global Medical Affairs, Bristol-Myers Squibb.
"These data demonstrate the positive clinical benefit that patients with advanced head and neck cancer may achieve with Erbitux, which is the first biologic ever approved by the FDA for head and neck cancer that showed a survival benefit in locally or regionally advanced SCCHN," said Eric K Rowinsky, chief medical officer and executive vice president of ImClone.
A comprehensive safety analysis was not performed at five years. The most common adverse events reported at three years in the Erbitux plus radiation treatment group included skin rash (87 per cent), mucositis/stomatitis (93 per cent), dysphagia (65 per cent), xerostomia (72 per cent), fatigue/malaise (56 per cent) and infusion reactions (15 per cent). Severe (Grade 3/4) adverse events included skin rash (17 per cent), mucositis/stomatitis (56 per cent), dysphagia (26 per cent), xerostomia (45 per cent), fatigue/malaise (4 per cent) and infusion reactions (3 per cent). With the exception of skin rash and infusion reactions (which were higher in the Erbitux-treated arm), the incidence of grade three or greater toxicity, including mucositis, which often precludes combining new therapies with radiation, did not differ significantly between the treatment arms.
The three-year results from this study and other Erbitux data were included in regulatory applications in various countries, including a supplemental Biologics License Application (sBLA) approved by the US Food and Drug Administration (FDA) in 2006.
Erbitux (cetuximab) is a monoclonal antibody (IgG1 Mab) designed to inhibit the function of a molecular structure expressed on the surface of normal and tumour cells called the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1).
ImClone Systems Incorporated is a fully integrated biopharmaceutical company committed to advancing oncology care by developing and commercializing a portfolio of targeted biologic treatments designed to address the medical needs of patients with a variety of cancers.
Bristol-Myers Squibb is a global biopharmaceutical and related health care products company whose mission is to extend and enhance human life.