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Addition of Cetuximab to Postoperative Radiotherapy in Intermediate-Risk Head and Neck Cancer


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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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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