The addition of zalutumumab, an investigational epidermal growth factor receptor (EGFR) inhibitor, to primary chemoradiotherapy did not increase locoregional control or improve survival at 3 years in patients with squamous cell carcinoma of the head and neck compared with chemoradiotherapy alone, according to the first results of a randomized phase III trial reported at the Presidential Session of the 2013 European Cancer Congress in Amsterdam.
Study Background
Cetuximab (Erbitux), an older EGFR inhibitor, is approved by the U.S. Food and Drug Administration for head and neck squamous cell carcinoma. When added to radiotherapy, cetuximab improves overall survival and locoregional disease control in this setting.
Preclinical study suggested that zalutumumab had good activity in head and neck squamous cell carcinoma when combined with radiotherapy. The Danish Head and Neck Cancer Group (DAHANCA) 19 trial was conducted to determine whether the addition of zalutumumab during radiotherapy could improve outcome in patients with head and neck squamous cell carcinoma, explained lead author Jesper G. Eriksen, MD, of Odense University Hospital, Denmark.
DAHANCA 19 Design
The study enrolled 619 patients with biopsy-verified head and neck squamous cell cancer from November 2007 to June 2012. Sites of cancer were oropharynx (69%), hypopharynx (12%), larynx (15%), and oral cavity (4%). Patients were stratified by tumor site, stage (89% stage III/IV), human papillomavirus/p16 status (75% of oropharyngeal carcinomas were positive), and concurrent cisplatin (70% of patients).
Intensity-modulated radiotherapy was given to all patients, and those with stage III/IV carcinomas were given concurrent weekly cisplatin at 40 mg/ m2. The radiosensitizer nimorazole (not available in the United States) was given 90 minutes prior to radiation. Patients were randomly assigned to identical chemoradiation with or without zalutumumab. The median duration of observation was 36 months.
Both treatment arms were well balanced for baseline demographic and disease characteristics; 97% of patients were treated with at least 66 Gy radiotherapy, and 97% were offered nimorazole.
Key Findings
At the time of data cutoff for the interim analysis, 126 locoregional events had occurred; 71 patients had died due to head and neck squamous cell carcinoma, and 45, from other causes.
No difference was seen between arms in the rate of locoregional control: The 3-year locoregional control rate was 78% in the zalutumumab arm vs 79% in controls.
When overall results were analyzed according to p16 status, locoregional control was improved in p16-positive patients (83% vs 73% in those who were p16-negative). However, p16 status had no effect on locoregional control in patients who received zalutumumab: 83% in p16-positive patients in both arms and 83% in p16-negative patients in both arms. Disease-specific survival and overall survival were comparable between the two arms.
The strongest prognostic factor in the overall trial was p16-positive status. Performance status as well as tumor and nodal stage were also prognostic.
Patients randomly assigned to zalutumumab had more mucositis than controls, and a significant increase in folliculitis (94% any grade and grade 3/4, 29% in the zalutumumab arm). Overall, 11% of patients withdrew from zalutumumab therapy due to skin rash. ■
Disclosure: Dr. Eriksen reported no potential conflicts of interest.
Reference
1. Eriksen JG, Maare C, Johansen J, et al: DAHANCA 19: First results of a randomized phase III study of the importance of the EGFR-inhibitor zalutumumab for the outcome of primary curative radiotherapy for squamous cell carcinoma of the head and neck. 2013 European Cancer Congress. Abstract 12. Presented September 30, 2013.
