FDA Approves Cetuximab for Metastatic Head and Neck Cancer

Roxanne Nelson

November 07, 2011

November 7, 2011 — The US Food and Drug Administration (FDA) has approved cetuximab (Erbitux, Bristol-Myers Squibb ) for use in combination with chemotherapy for the treatment of metastatic head and neck cancer.

Data show that when combined with cisplatin-based chemotherapy, cetuximab improved overall survival, compared with chemotherapy alone. According to the researchers, this is the first time in 3 decades — since cisplatin was first used in head and neck cancer — that any regimen has improved on its success. The improved survival that was seen after cetuximab was added to the regimen (at a median of 2.7 months) is "therefore notable."


Cetuximab was approved in the United States in 2004 for the treatment of epidermal growth-factor receptor–positive late-stage colon cancer in patients who no longer responded to chemotherapy. In 2006, it was approved for use in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. This latest approval expands on that to cover metastatic head and neck cancer.

The ability of cetuximab "to extend the lives of patients with head and neck cancer is an important tool for oncologists, who often rely on a multitreatment approach for patients," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, in a 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."


The safety and effectiveness of cetuximab for this indication is based on the results of a multicenter clinical study — the Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME) trial. The results of this study were first reported at the 2007 meeting of the American Society of Clinical Oncology. At the time, experts in the field predicted that they would change clinical practice. The results were subsequently published in 2008 (N Engl J Med. 2008;359:1116-1127).

Cetuximab was granted approval by the European Commission in November 2008 for the treatment of first-line recurrent and/or metastatic head and neck cancer on the basis of the EXTREME study.

The trial involved 442 patients with untreated recurrent or metastatic squamous cell carcinoma of the head and neck; approximately 60% of the cohort had not received any previous chemotherapy. All patients received chemotherapy with a platinum agent (cisplatin or carboplatin, chosen by the investigator) plus infusional 5-fluorouracil. Half of the patients were randomized to also receive cetuximab.

On average, patients who received cetuximab plus chemotherapy survived longer than those who received chemotherapy alone (10.1 vs 7.4 months; hazard ratio [HR] for death, 0.80; P = .04).

The addition of cetuximab also significantly improved median progression-free survival (3.3 vs 5.6 months; HR for progression, 0.54; P < .001) and increased the response rate (20% vs 36%; P < .001).

"I think these data support the notion that we have a new standard treatment for patients with recurrent and/or metastatic head and neck cancer," lead researcher Jan Vermorken, MD, PhD, professor of oncology at Antwerp University Hospital, in Ghent, Belgium, told Medscape Medical News when the study was published. "I would recommend that every patient with recurrent head and neck cancer who is not a candidate for radiation or surgery now receive platinum-based chemotherapy plus cetuximab, if their condition allows them to tolerate this."

Higher Risk Adverse Events

The most commonly reported adverse events in patients who received cetuximab included rash, pruritus, nail changes, headache, diarrhea, and respiratory, skin, and mouth infections. The addition of cetuximab also increased the rate of sepsis, which occurred in 9 patients treated with chemotherapy plus cetuximab but in only 1 patient treated with chemotherapy alone (P = .02).

Cetuximab has also been known to cause low serum magnesium, potassium, and calcium; in this study, the incidence of hypomagnesemia also increased (11 patients treated with chemotherapy plus cetuximab and 3 treated with chemotherapy alone; P = .05). Other adverse events, such as neutropenia, were reported at similar rates in both groups, and the authors note that these adverse effects are consistent with the adverse-effect profile of cetuximab.


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