FDA Approves Cetuximab for Late-Stage Head and Neck Cancer

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for "recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU," according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for "locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy," and for "recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

"Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. "Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible," he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study "and other clinical trial data establish the efficacy of Erbitux at the recommended dose," according to the revised prescribing information posted on the FDA Web site.

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for "recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU," according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for "locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy," and for "recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

"Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. "Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible," he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study "and other clinical trial data establish the efficacy of Erbitux at the recommended dose," according to the revised prescribing information posted on the FDA Web site.

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for "recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU," according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for "locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy," and for "recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

"Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. "Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible," he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study "and other clinical trial data establish the efficacy of Erbitux at the recommended dose," according to the revised prescribing information posted on the FDA Web site.