Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer
Authors: Mitchell Machtay, Pedro A. Torres-Saavedra, Wade Thorstad, Phuc Felix Nguyen-Tân, Lillian L. Siu, F. Christopher Holsinger, Adel El-Naggar, Christine Chung, Anthony Cmelak, Barbara Burtness, Greg Bednarz, Harry Quon, Stephen L. Breen, Clement K. Gwede, Adam P. Dicker, Min Yao, Richard C. Jordan, Jennifer Dorth, Nancy Lee, Jason W. Chan, Neal Dunlap, Voichita Bar-Ad, William A. Stokes, Arnab Chakravarti, David Sher, Shyam Rao, Jonathan Harris, Sue S. Yom, Quynh-Thu Le, Voichita Bar-Ad, Greg Bednarz, Daniel W. Bowles, Stephen Breen, Barbara Burtness, Arnab Chakravarti, Jason Chan, Christine Chung, Anthony Cmelak, Adam P. Dicker, Jennifer Dorth, Neal Dunlap, Adel El-Naggar, Clement K. Gwede, Jonathan Harris, F. Christopher Holsinger, Christopher U. Jones, Richard C. Jordan, Greg A. Krempl, Quynh-Thu Le, Nancy Lee, Christopher Lominska, Daniel J. Ma, Mitchell Machtay, Loren K. Mell, Phuc Felix Nguyen-Tan, Harry Quon, Adam Raben, Shyam Rao, Stuart Samuels, David Sher, Lillian L. Siu, Sharon Spencer, William A. Stokes, Vinita Takiar, Wade Thorstad, Pedro Torres-Saavedra, Christopher T. Wilke, Min Yao, Sue S. Yom, Melissa R. Young
Journal: Journal of Clinical Oncology (2025)

PURPOSE Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer. METHODS Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)–negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test. RESULTS We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided P = .0747; 5-year OS 76.5% v 68.7%), but DFS was (HR, 0.75; one-sided P = .0168; 5-year DFS 71.7% v 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided P &lt; .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided P = .3101). There were no grade 5 toxicities in either arm. CONCLUSION RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.