In a phase III trial (NRG/RTOG 0920) reported in Journal of Clinical Oncology, Machtay et al found that the addition of cetuximab to postoperative radiotherapy significantly improved disease-free survival—but not overall survival—in patients with completely resected, intermediate-risk, squamous cell carcinoma of the head and neck.
Study Details
In the open-label multicenter trial, 577 patients enrolled between November 2009 and March 2018 were randomly assigned to receive postoperative intensity-modulated radiotherapy plus cetuximab (n = 290) or radiotherapy alone (control group, n = 287). Postoperative radiotherapy was given at 60 Gy in once-daily fractions of 2 Gy, with an optional sequential boost of 6 Gy in three fractions to regions of close resection margins. Cetuximab was given at a loading dose of 400 mg/m2 at 7 to 10 days before the start of radiotherapy and then once weekly at 250 mg/m2 throughout radiotherapy and 4 weeks after completion of radiotherapy. The primary endpoint was overall survival; disease-free survival was a secondary endpoint.
Key Findings
Median follow-up was 7.2 years (interquartile range = 5.1–9.2 years). Overall, fewer deaths than expected were observed (n = 184). The stratified hazard ratio [HR] for overall survival for the radiotherapy/cetuximab group vs the control group was 0.81 (95% confidence interval [CI] = 0.60–1.08, P = .0747). Overall survival rates were 83.4% vs 76.4% at 3 years and 76.5% vs 68.7% at 5 years. No significant differences between groups were observed among patients with human papillomavirus (HPV)-negative disease (80% of study population) or among those with HPV-positive disease.
The radiotherapy/cetuximab group had significantly better disease-free survival vs the control group (stratified HR = 0.75, 95% CI = 0.57–0.98, P = .0168). Disease-free survival rates were 78.3% vs 71.5% at 3 years and 71.7% vs 63.6% at 5 years. A significant benefit in the radiotherapy/cetuximab group was observed in patients with HPV-negative disease, with no significant difference between groups observed among patients with HPV-positive disease.
Grade 3 or 4 treatment-related acute toxicity was observed in 70.3% of the radiotherapy/cetuximab group vs 39.7% of the control group (P < .0001); the most common adverse events in both groups were oral mucositis (38.0% vs 21.6%), dysphagia (21.7% vs 13.1%), and radiation dermatitis (17.0% vs 6.4%). Late grade ≥ 3 toxicity was observed in 33.2% vs 29.0% of patients (P = .3101), most commonly dysphagia in both groups (12.3% vs 8.6%). No treatment-related deaths were observed.
The investigators concluded: “Radiotherapy [+ cetuximab] significantly improved [disease-free survival], but not [overall survival], with no increase in long-term toxicity, compared with [radiotherapy] alone for resected, intermediate-risk [squamous cell carcinoma of the head and neck]. Radiotherapy [+ cetuximab] is an appropriate option for carefully selected patients with HPV-negative disease.”
Mitchell Machtay, MD, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute and Eli Lilly, Inc. For full disclosures of all study authors, visit the Journal of Clinical Oncology.