Clinical data presented at the 2026 American Society for Radiation Oncology Annual Meeting in Boston shows that weekly cisplatin combined with radiation fails to reduce acute toxicity compared with a standard every-three-week dosing schedule for patients with p16-negative locally advanced head and neck cancer. Researchers evaluated 234 eligible patients in the Phase II portion of the NRG-HN009 trial, finding similar overall burdens of serious acute treatment-related side effects between the two regimens alongside distinct toxicity profiles.
Trial Design and Patient Stratification in NRG-HN009
Physicians typically treat locally advanced head and neck cancer using either a higher dose of cisplatin every three weeks or a lower dose weekly alongside radiation. Prior to the NRG-HN009 trial, randomized evidence comparing cancer control and side effects for these regimens remained limited. This gap proved particularly critical for patients with p16-negative disease, who frequently present with multiple comorbidities and lower tolerance for intensive chemoradiation regimens.
The Phase II trial enrolled 234 eligible patients diagnosed with p16-negative squamous cell carcinoma of the head and neck. Investigators stratified participants by Zubrod Performance Score, smoking history, tumor stage, and age. Patients were then randomly assigned to receive 70 Gy of radiation therapy combined with either 100 mg/m² of cisplatin every three weeks or 40 mg/m² of cisplatin weekly. Trial records show that 91% of treated patients completed the required six-month follow-up.
Toxicity Endpoints and Adverse Event Profiles
The primary endpoint of the NRG-HN009 study measured acute toxicity using a T-score, defined as the total number of treatment-related grade 3-4 adverse events occurring during treatment or within six months afterward. Results revealed a mean T-score ratio of 1.11 with a 90% upper confidence bound of 1.33 and p=0.77. The mean T-score reached 2.23 for the every-three-week arm and 2.48 for the weekly arm.
While overall severe toxicity burdens were similar, the two arms produced notable differences in specific side effect rates of at least 5%. The every-three-week cisplatin arm exhibited higher rates of grade 3-4 nausea, dehydration, and acute kidney injury. Conversely, the weekly cisplatin arm showed higher rates of white blood cell count reductions and decreased magnesium levels. Six-month locoregional failure rates reached 4.6% in the every-three-week arm compared to 9.6% in the weekly treatment arm, yielding an absolute difference of 5.0%.
Implications for Future Advanced Cancer Care
Because the trial did not meet its predefined statistical criteria for reduced acute toxicity with the weekly schedule, the p16-negative cohort did not advance to the Phase III portion of the NRG-HN009 protocol. Paul Harari, MD, a researcher at the University of Wisconsin and lead author of the manuscript, noted that the data demonstrates similar overall burdens of serious acute side effects between the two schedules while highlighting divergent toxicity profiles.
National Institutes of Health grants supporting the trial included National Cancer Institute awards U10CA180868, U10CA180822, UG1CA189867, U24CA180803, CTEP, 3UG1CA189830, 3UG1CA189821, 3UG1CA239767, and 5UG1CA239758. Authors noted that the content remains their sole responsibility and does not necessarily represent official views of the National Institutes of Health.
Common Questions About the NRG-HN009 Trial
What was the primary goal of the NRG-HN009 trial?
The trial aimed to determine whether a weekly low-dose cisplatin regimen combined with radiation reduced acute toxicity compared to the standard every-three-week high-dose cisplatin regimen in patients with p16-negative locally advanced head and neck cancer.
Why did the p16-negative cohort not advance to Phase III?
The study failed to meet its predefined statistical criteria showing significantly lower acute toxicity for the weekly cisplatin schedule compared with the every-three-week schedule.
What specific side effects differed between the two dosing arms?
Patients receiving cisplatin every three weeks experienced higher rates of grade 3-4 nausea, dehydration, and acute kidney injury. Patients receiving weekly cisplatin experienced higher rates of decreased white blood counts and lower magnesium levels.
What were the locoregional failure rates at six months?
The six-month locoregional failure rate was 4.6% in the every-three-week treatment arm and 9.6% in the weekly treatment arm.
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