Recent results from the phase III NRG Oncology RTOG 0920 (NRG-RTOG 0920) trial assessing postoperative radiotherapy with or without concurrent cetuximab for selected patients with squamous cell cancer of the head and neck (SCCHN) showed that radiotherapy with cetuximab demonstrated superiority as measured by improved disease-free survival, a secondary endpoint. The study also showed no increase in long-term toxicity. The trial results, however, did not show a statistically significant improvement in overall survival, the primary endpoint. These results were recently published in the Journal of Clinical Oncology, one of the highest impact cancer journals in the world.
"Currently, the outcomes for patients with HPV-negative SCCHN remain poor and treatment is associated with a high rate of locoregional failure and death, despite surgical resection with postoperative radiotherapy," stated Mitchell Machtay, MD, of the Pennsylvania State University Cancer Institute and the lead author of the NRG-RTOG 0920 manuscript. "Given that EGFR is a common hallmark of SCCHN, our hope was that adding cetuximab to postoperative radiotherapy could help improve outcomes for these patients without the burden of additional long-term toxicity."
NRG-RTOG 0920 enrolled 577 eligible patients with SCCHN of the oral cavity, oropharynx, or larynx, and with one or more intermediate-risk factors that warranted postoperative radiotherapy, but not high dose cisplatin chemotherapy. Most tumors (85%) had high EGFR expression. Patients were randomly assigned to receive either IMRT (60-66 Gy) with weekly cetuximab (C+RT) or radiotherapy alone (RT). The primary objective of this trial was to determine if the addition of cetuximab to radiotherapy improved overall survival. Disease-free survival and toxicity were secondary endpoints.
Overall survival at a median follow-up of 7.2 years was not significantly improved (hazard ratio [HR] 0.81; one-sided p=0.075; 5-year estimates 76.5% for C+RT and. 68.7% for RT alone) but disease-free survival was (HR 0.75; one-sided p=0.017; 5-year estimates 71.7% for C+RT and 63.6% for RT alone). The benefit discovered with the addition of cetuximab was only seen in the HPV-negative subpopulation (80 % of the patients in the trial). Grade 3-4 acute toxicity rates were 39.7% (RT) and 70.3% (C+RT) (two-sided p<0.0001) and late grade 3-4 toxicity rates were 29.0% (RT) and 33.2% (C+RT) (two-sided p=0.31 ). There were no grade 5 (fatal) toxicities in either arm.
"These data would indicate that adding cetuximab to radiotherapy is an appropriate option for carefully selected patients with HPV-negative disease," Dr. Machtay added, 'particularly those for whom cisplatin-based chemotherapy with radiationis not a good choice"
This project was supported by grants U10CA180868 (NRG Oncology Operations), UG1CA189867 (NCORP), U10CA180822 (NRG Oncology SDMC), U24CA196067 (NRG Oncology Specimen Bank), U24CA180803 (IROC), all from the National Cancer Institute (NCI), part of the National Institutes of Health. Grant support was also obtained from Eli Lilly, Inc.
Citation
Machtay M, Torres-Saavedra PA, Thorstad W, Nguyen-Tân PF, Siu LL, Holsinger FC, El-Naggar A, Chung C, Cmelak A, Burtness B, Bednarz G, Quon H, Breen SL, Gwede CK, Dicker AP, Yao M, Jordan RC, Dorth J, Lee N, Chan JW, Dunlap N, Bar-Ad V, Stokes WA, Chakravarti A, Sher D, Rao S, Harris J, Yom SS, Le QT; NRG Oncology RTOG 0920 Collaborating Team; TransSCOT Consortium. Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer. J Clin Oncol. 2025 Jan 22:JCO2401829. doi: 10.1200/JCO-24-01829. Epub ahead of print. PMID: 39841939.
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology's extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI's National Clinical Trials Network.
