BOSTON, MA – Physicians typically use either a higher dose of cisplatin given every three weeks or a lower dose given weekly in combination with radiation to treat locally advanced head and neck cancer. However, prior to NRG-HN009, there was limited randomized evidence to determine which regimen provided the best balance of cancer control and treatment-related side effects. This question is particularly important for patients with p16-negative disease, who often have multiple comorbidities and may have a lower tolerance for intensive chemoradiation. The Phase II portion of NRG-HN009 compared these two treatment regimens in patients with p16-negative disease and found that weekly cisplatin failed to show significantly lower acute toxicity compared with cisplatin given every three weeks. Because the study did not meet its predefined criteria for reduced acute toxicity with weekly cisplatin, the p16-negative cohort did not advance to the Phase III portion of the trial. These results were presented during the Late-Breaking Abstract Session of the 2026 American Society for Radiation Oncology Annual Meeting in Boston, Massachusetts.
“These findings provide important evidence that weekly cisplatin induces a similar overall burden of serious acute treatment-related toxicity compared with the standard every-three-week schedule in patients with p16-negative locally advanced head and neck cancer. However, the two treatment approaches resulted in different profiles of side effects. These results underscore the need for future research to identify more individualized treatment strategies that can reduce toxicity while maintaining effective cancer control for advanced head and neck cancer patients,” stated Paul Harari, MD at the University of Wisconsin and the lead author of the NRG-HN009 manuscript.
This Phase II trial accrued 234 eligible patients with p16-negative squamous cell carcinoma of the head and neck and stratified them by Zubrod Performance Score, smoking history, tumor stage, and age then randomly assigned to receive either 70 Gy RT with 100 mg/m2 of cisplatin every 3 weeks (Q3) or 70 Gy RT with 40 mg/m2 of cisplatin weekly (Q1). Of the patients treated on the trial, 91% completed 6-month follow-up.
The primary endpoint of NRG-HN009 was acute toxicity as measured by T-score. This was defined as the number of all treatment-related grade 3-4 adverse events during treatment or within 6 months of treatment. The mean T-score ratio was 1.11 (90% upper confidence bound 1.33; p=0.77) with mean T-scores of 2.23 (95% confidence interval 1.81, 2.65) for the Q3 treatment arm and 2.48 (95% CI 1.97, 2.99) for Q1 treatment arm. There were several differences in the profile of acute grade 3-4 adverse event rates between arms of ≥ 5%. The Q3 treatment arm displayed higher grade 3-4 toxicity rates of nausea, dehydration, and acute kidney injury. The Q1 treatment arm showed higher toxicity rates of white blood count and magnesium decrease. 6-month locoregional failure rates were 4.6% in the Q3 treatment arm and 9.6% in the Q1 treatment arm [absolute difference 5.0% (95% CI 1.0, 8.9)].
This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NRG NCORP), U24CA180803 (IROC), CTEP, 3UG1CA189830 (Heartland NCORP), 3UG1CA189821 (Kaiser NCORP), 3UG1CA239767 (Kansas NCORP) and 5UG1CA239758 (National Capital Area NCORP) from the National Cancer Institute (NCI), part of National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Citations
Harari PM, Attwood K, Siddiqui F, Holmes B, Chung CH, Katzel JA, Witek ME, Sharon J, Bratman S, Wilkins M, Dorth J, Burr A, Olazagasti C, Singh AK, Goodman BD, Razavian N, Harris J, Le QT, Yom SS. NRG-HN009 Randomized Phase II/III Trial of RT + Cisplatin Q3 Weeks vs RT + Cisplatin Weekly for Patients with Locoregionally Advanced SCCHN: p16-Negative Phase II Acute Toxicity Results. Paper presented during the Late-Breaking Abstract Session at the annual meeting of the American Society for Radiation Oncology. Boston, MA. (2026, September).
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 emphasis on sex-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. www.nrgoncology.org