NEW ORLEANSCetuximab (Erbitux) plus high-dose radiation therapy (RT) significantly improved survival in patients with advanced head and neck cancer, compared with RT alone, according to results of an international phase III trial reported at the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 5507).
James Bonner, MD, of the University of Alabama, Birmingham, reported a 54-month median survival for cetuximab(Drug information on cetuximab)/RT, compared with 28 months for RT only (P = .02) in patients with locoregionally advanced squamous cell carcinoma of the head and neck. Besides the near doubling of survival, locoregional control was achieved for a median of 36 months with cetuximab/RT vs 19 months for RT alone (P = .02).
The cetuximab antibody is known to block the epidermal growth factor receptor (EGFR). Researchers hypothesized that cetuximab would be beneficial in this patient population, since most head and neck cancer cells heavily express EGFR. Overexpression of EGFR has been associated with poor clinical outcomes and aggressive tumor behavior, Dr. Bonner said. In preclinical tumor models, EGFR inhibition was shown to enhance the effects of radiation, and subsequent phase I/II clinical results with cetuximab/RT were promising.
The phase III cetuximab/RT study included 424 patients (median age, 57 years; 80% male) with locoregionally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. About 80% had tumors expressing EGFR. Patients were randomized to radiation alone or radiation plus cetuximab, and were followed for a median of 38 months.
Median survival and locoregional control were both significantly improved with cetuximab. The percentage of patients who achieved locoregional control at 1 and 2 years following treatment was 69% and 56%, respectively, in cetuximab-treated patients, compared with 59% and 48% for those treated with RT alone (P = .02). Likewise, the percentage of patients alive at 2 and 3 years post-treatment was 62% and 57%, respectively, for the cetuximab group vs 55% and 44% for the RT-alone group (P = .02).
Investigators observed an increase in skin reactions with cetuximab that has been previously reported in patients who receive anti-EGFR agents. However, this side effect did not interfere with delivery of radiotherapy and healed after completion of treatment. Infusion reactions were also more common in the cetuximab arm. Importantly, however, adding cetuximab did not appear to increase the incidence of radiation-induced side effects, such as mucositis and dysphagia.
"The use of cetuximab and radiation therapy may become an excellent choice of therapy for this group of patients," Dr. Bonner concluded. "Future studies should be performed to examine combinations of chemotherapy, radiation therapy, and cetuximab." In fact, such investigations are underway, including a pilot study of chemotherapy, radiotherapy, and cetuximab performed at Memorial Sloan-Kettering Cancer Center. "We will look forward to seeing the results," Dr. Bonner said
Harlan Pinto, MD, of Stanford University Medical Center, commented that adding cetuximab to radiotherapy provided a magnitude of impact on survival that "may be comparable to conventional chemotherapy alternatives; it may mean that treatment with more toxic chemotherapy may be unnecessary."