By Christopher Wilke, MD, PhD, and Yvonne Mowery, MD, PhD, University of Pittsburgh
The NRG-HN009 trial represents a long-overdue attempt to resolve one of the most persistent debates in head and neck oncology: which cisplatin schedule — high-dose every three weeks or low-dose weekly — should be paired with definitive radiotherapy? This question has divided practitioners for years, with institutions and individual oncologists harboring strong preferences based upon relatively sparse data. As the study’s principal investigator Paul Harari, MD, FASTRO, notes, "We owe this information to our H&N patients to help establish whether one regimen or the other is ‘best’ or to confirm that they are equivalent.”
The phase II toxicity results for the study’s p16-positive cohort, presented for the first time at the 2026 Multidisciplinary Head and Neck Cancers Symposium, provide our initial glimpse into a possible answer to this critical question. Among 241 patients randomized to receive definitive chemoradiotherapy with 70 Gy and concurrent cisplatin with either 100 mg/m² administered every three weeks or 40 mg/m² given weekly, the primary endpoint —mean T-score reflecting cumulative grade 3-4 adverse events — did not differ significantly between the arms (2.38, 95% CI: 1.99-2.77 vs. 2.48, 95% CI: 2.09-2.87, respectively). The trial did not meet its prespecified criteria to advance the p16-positive cohort to phase III, as the weekly arm failed to demonstrate significantly lower toxicity.
The most clinically meaningful finding, however, may lie in further examination of the toxicity profiles rather than the overall mean T-scores. The every-three-week regimen produced a greater incidence of grade 3-4 radiation dermatitis (10% vs. 1%), acute kidney injury (10% vs. 1%) and hearing impairment (5% vs. 1%), while patients receiving the weekly schedule experienced more leukopenia (24% vs. 14%), anorexia (16% vs. 9%), pain (10% vs. 3%), thrombocytopenia (4% vs. 0%), and fatigue (8% vs. 1%).
The comparable six-month locoregional failure rates (3.5% for every-three-weeks vs. 2.7% for weekly) provide early reassurance that disease control was not compromised by either approach, though longer follow-up is essential.
Several important caveats deserve emphasis. First, these results reflect only p16-positive patients — the p16-negative cohort completed enrollment in September 2025 with those results expected to be released later this year. Second, the T-score methodology, while comprehensive in capturing grade 3-4 events, may not sufficiently account for the varying impact different toxicities have on function and quality of life. As Dr. Harari notes, “While this represents our first look at the acute toxicity profiles, there will be several potentially very important secondary endpoints that will emerge over the next year and beyond.” Longer term follow-up with the inclusion of additional study data such as audiograms and patient-reported quality of life metrics will be very revealing in assessing differences in these domains between the study arms.
Although these findings will not immediately change clinical practice, particularly with the p16-negative results still pending, they provide valuable data for shared decision making for patients and clinicians alike.
As the head and neck community continues to grapple with treatment personalization in the absence of validated biomarkers for de-intensification for p16+ disease, NRG-HN009 reminds us that progress sometimes comes not from dramatic breakthroughs, but rather from careful, systematic evaluation of existing approaches. Understanding which schedule best serves individual patients represents meaningful progress toward individualized care, even if both schedules ultimately prove effective for the broader population.
More on NRG HN009
The NRG Oncology Podcast recently interviewed Dr. Harari on the initial toxicity results of NRG-HN009, reported during the Multidisciplinary Head and Neck Cancer Symposium. Podcast co-hosts, Stephen Chun, MD, and Lauren Henke, MD, MS, dive into the design of the study, the results that were presented today, and how these results shape future research measures in this space.
This podcast will be available following the presentation at 12:20 p.m. Pacific time. You can listen to this episode on Spotify, Apple Music, Amazon, and YouTube or you can stream directly from the NRG Oncology website at www.NRGOncology.org/Podcast.
Published February 20, 2026
