Erbitux Wins Approval for Squamous Cell H&N Cancer

April 1, 2006

The FDA has approved the marketing of the first new drug for the treatment of head and neck cancer in nearly half a century and granted it two indications.

ROCKVILLE, Maryland—The FDA has approved the marketing of the first new drug for the treatment of head and neck cancer in nearly half a century and granted it two indications. Erbitux (cetuximab, ImClone Systems) won approval in combination with radiation for the treatment of patients with unresectable squamous cell carcinoma of the head and neck (SCCHN) and as monotherapy for the treatment of SCCHN that has metastasized despite prior use of platinum-based chemotherapy.

"We consider this approval an important advance in the treatment of head and neck cancer because it has been shown to help some patients live longer," said Steven Galson, MD, director of FDA's Center for Drug Evaluation and Research. "Patients need as many effective treatment options as possible."

FDA said Erbitux is the first drug approved for treating head and neck cancer "since methotrexate became available in the 1950s." The drug won approval as a SCCHN treatment based on a pivotal phase III study that showed it prolonged survival 20 months longer than radiation therapy alone. "This is an important milestone" said Kie-Kian Ang, MD, PhD, of M.D. Anderson Cancer Center. "For patients with locally or regionally advanced disease, Erbitux in combination with radiation therapy has demonstrated a clinically significant improvement in survival and locoregional control."

The monotherapy indication for metastatic head and neck cancer resulted from a study that found evidence of tumor shrinkage in 13% of Erbitux-treated patients, who had an average duration of response of 6 months.

FDA previously approved Erbitux for use in combination with irinotecan (Camptosar) for the treatment of patients with EGFR-expressing metastatic colorectal cancer and as a monotherapy for patients intolerant to irinotecan.

The phase III pivotal trial of Erbitux plus radiation therapy involved 424 patients with locally or regionally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx and no prior therapy. Patients were randomized to receive Erbitux plus radiation or radiation alone. The Erbitux arm received an initial dose (400 mg/m2) one week before the initiation of radiation, and continued on weekly doses (250 mg/m2) throughout the patient's 6- to 7-week course of radiotherapy. Patients received 1 to 11 drug doses (median, 8) during the trial.

The results showed a 9.5 month (32%) improvement in the median duration of locoregional control for the Erbitux arm vs the radiation-only group (24.4 months vs 14.9 months, P = .005). The Erbitux-treated patients also had a median survival time 19.7 months longer (26%) than the radiation-only arm (49 months vs 29.3 months, P = .03).

To support the drug's use as a single- agent treatment, the sponsor submitted a single-arm multicenter phase II trial. In this study, researchers treated 103 patients with recurrent or metastatic SCCHN whose disease was not suitable for further local therapy and who had failed platinum-based chemotherapy. The patients received Erbitux until disease progression or unacceptable toxicity. The median number of doses was 11 (range, 1 to 45). The clinically meaningful response rate was 13%, with a median duration of response of 5.8 months.

ImClone developed and manufactures Erbitux; Bristol-Myers Squibb markets and distributes the drug. "Pretreatment assessment for evidence of EGFR expression is not required for patients with squamous cell carcinoma of the head and neck," the two companies said in a joint statement announcing the approval.