Cetuximab (Erbitux®) Plus Chemo Extends Survival in Advanced Head and Neck Cancer
Patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received cetuximab (Erbitux®) in addition to standard chemotherapy lived about three months longer than those receiving chemotherapy alone.
American Society of Clinical Oncology (ASCO) annual meeting, Chicago, June 2, 2007; final results subsequently published in the Sept. 11, 2008, New England Journal of Medicine (see the journal abstract).
Patients with stage III/IV squamous cell carcinoma of the head and neck (SCCHN) have cancer that has returned (recurrent) or spread to distant organs (metastatic). For more than two decades, the standard of care for such patients has included chemotherapy, either to treat the cancer or to provide relief from symptoms (palliative care). Such chemotherapy currently involves one of the platinum drugs (carboplatin or cisplatin), and generally extends their lives only about six or seven months.
Most head and neck cancer cells overexpress (make too much of) a protein called the epidermal growth factor receptor (EGFR), which may help cancer cells grow more aggressively. Cetuximab is a targeted biological therapy - a monoclonal antibody that specifically attaches to and blocks EGFR. It is approved by the U.S. Food and Drug Administration for the treatment of advanced head and neck cancer, either alone or in combination with radiotherapy.
The study described here investigated whether cetuximab in combination with chemotherapy might also prove beneficial for this group of patients
The EXTREME (Erbitux in First-Line Treatment of Recurrent or Metastatic Head & Neck Cancer) study is a European multicenter phase III trial to determine whether adding cetuximab improves the impact of platinum-based chemotherapy.
Between December 2004 and March 2007, researchers enrolled 442 patients in 17 countries who had stage III or IV recurrent and/or metastatic SCCHN, and who were not candidates for further surgery or radiation . About half of the patients had cancer in their pharynx (throat), and a quarter in their larynx (voice box), but none in the nasopharynx (upper part of the throat). The patients averaged 57 years of age. Only about 10 percent were women.
Patients were randomly assigned to receive either chemotherapy (222 patients) or the same chemotherapy with cetuximab (220 patients). Chemotherapy consisted of 5-fluorouracil plus either carboplatin or cisplatin.
The trial was led by Jan Vermorken, M.D., Ph.D., of the University of Antwerp in Belgium. Vermmorken as well as other researchers involved in the trial have various relationships with Merck KGaA, Amgen, Oxygene, and sanofi-aventis. Merck KGaA provided funding for the study. (See the protocol summary.)
Patients treated with cetuximab reduced their risk of dying by 20 percent, surviving a median of 10.1 months compared to 7.4 months for those receiving chemotherapy alone.
Patients getting cetuximab had more vomiting and diarrhea, but otherwise their side effects didn’t differ much from those getting chemotherapy alone.
“This survival benefit is among the largest ever seen” in studies of this patient population, said Vermorken. “With new targeted agents such as cetuximab, we are on the brink of changing the way we treat patients with head and neck cancers.” Marshall R. Posner, M.D., of the Dana-Farber Cancer Institute in Boston, Mass., agreed, adding that this study is the “first demonstration of a survival improvement in the palliative setting for any therapy in head and neck cancer.”
Posner also remarked that the current standard chemotherapy cannot be used long-term because many patients eventually develop numbness and problems with their immune system. “Cetuximab can be continued for longer” said Posner, “and thus be more effective for palliation.”
“This result joins others as part of a paradigm shift. We are beginning to incorporate these new biological targeted agents into current standard-of-care chemotherapy,” said C. Norman Coleman, M.D., a senior principal investigator in the Radiation Oncology Branch of National Cancer Institute’s Center for Cancer Research.