FDA Approves Cetuximab to Treat Head and Neck Cancer

ImClone Systems Incorporated and Bristol-Myers Squibb Company recently announced that the US Food and Drug Administration (FDA) has approved cetuximab (Erbitux), an immunoglobulin (Ig)G1 monoclonal antibody, for use in the treatment of squamous cell carcinoma of the head and neck. Designed to inhibit the function of the epidermal growth factor receptor (EGFR), cetuximab is the first and only monoclonal antibody to be approved for the treatment of head and neck cancer.

With this approval, cetuximab is indicated for use in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN) and as a single agent in recurrent or metastatic SCCHN where prior platinum-based chemotherapy has failed. These indications are based on a phase III study that demonstrated a survival and locoregional control advantage when cetuximab was added to radiation therapy, and a phase II study, where cetuximab therapy alone reduced tumor size.

Key Trials

In a pivotal, international, randomized phase III trial of 424 patients with locally or regionally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx with no prior therapy, the addition of cetuximab to radiation (n = 211) compared to radiation alone (n = 213) resulted in a 9.5-month improvement in median duration of locoregional control (24.4 vs 14.9 months, P = .005). Cetuximab was dosed weekly, starting 1 week before radiation and for the duration of radiation therapy, for a median of eight doses. Results also showed a 19.7-month improvement in median survival (49.0 vs 29.3 months, P = .03).

Another principal trial was a single-arm, multicenter, phase II trial studying the effects of cetuximab as a single-agent treatment. The study analyzed 103 patients with recurrent or metastatic SCCHN not suitable for further local therapy and who had failed platinum-based chemotherapy. Cetuximab was administered until disease progression or unacceptable toxicity. The median number of doses was 11. Patients demonstrated a clinically meaningful objective response rate of 13%, and the median duration of response was 5.8 months (range: 1.2-5.8 months).

Second Indicated Tumor Type

This is the second indicated tumor type for cetuximab, previously approved by the FDA for use in combination with irinotecan (Camptosar) for patients with EGFR-expressing metastatic colorectal cancer who are refractory to irinotecan therapy and as a single agent for the treatment of EGFR-expressing metastatic colorectal cancer in patients who are intolerant to irinotecan therapy. The effectiveness of cetuximab in treating EGFR-expressing metastatic colorectal cancer is based on objective response rates, but no data yet demonstrate an improvement in survival with cetuximab for the treatment of EGFR-expressing metastatic colorectal cancer.