Previous studies have found that when patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma are treated with radiotherapy plus cisplatin, they have high survival. The authors were interested in whether cisplatin could be replaced with cetuximab, an antibody against the epidermal growth factor receptor, and maintain this high survival while reducing treatment toxicity. They conducted a randomised, non-inferiority trial in the USA and Canada. Patients were eligible if they had histologically confirmed HPV-positive oropharyngeal carcinoma of clinical categories T1-T2, N2a-N3 M0 or T3-T4, N0-N3 M0; Zubrod performance status 0 or 1; aged ≥18 years; and had adequate bone marrow, hepatic and renal function. Patients were randomised (1:1) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin. Patients received either IV cetuximab at a loading dose of 400 mg/m2 5-7 days before radiotherapy initiation, followed by cetuximab 250 mg/m2 weekly for seven doses (total 2150 mg/m2), or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy (total 200 mg/m2). All patients received accelerated intensity-modulated radiotherapy at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 hours apart). The primary endpoint was overall survival. 849 patients were randomised . After a median follow-up of 4·5 years, the authors found that radiotherapy plus cetuximab did not meet non-inferiority criteria for overall survival (hazard ratio [HR] 1·45, 95% upper CI 1·94 for non-inferiority). The estimated 5-year overall survival was 77·9% in the cetuximab group versus 84·6% in the cisplatin group. Progression-free survival was significantly lower in the cetuximab group compared with the cisplatin group (67·3% vs. 78·4%; HR 1·72, 95%CI 1·29-2·29), and locoregional failure was significantly higher in the cetuximab group compared with the cisplatin group (17·3% vs. 9·9%; HR 2·05, 95%CI 1·35-3·10). The proportions of acute moderate to severe toxicity (77·4% vs. 81·7%) and late moderate to severe toxicity (16·5% vs. 20·4%) were similar between the cetuximab and cisplatin groups. Therefore for patients with HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab is inferior for overall survival and progression-free survival compared with radiotherapy plus cisplatin.
Read more here