Adjuvant Nivolumab + CRT Improves DFS in HNSCC

Medscape

02-06-2025

Adding nivolumab (Opdivo) to standard-of-care cisplatin radiotherapy (CRT) after surgery for locally advanced head and neck squamous cell carcinoma (HNSCC) in patients at a high risk for relapse reduced the risk for recurrence, as per a phase 3 trial.
This new therapeutic option 'improved high-risk locally advanced squamous cell carcinoma of the head and neck,' said study author Jean Bourhis, MD, PhD, during a press conference at American Society of Clinical Oncology (ASCO) 2025.
Postoperative nivolumab added to standard-of-care adjuvant CRT 'could be proposed as a new standard treatment for the first time in two decades,' said Bourhis, MD, PhD, of Lausanne University Hospital in Lausanne, Switzerland, while reporting results of NIVOPOSTOP (GORTEC 2018-01) during the press conference.
Agreeing with Bourhis' characterization of the therapeutic regimen followed in the new trial, Stuart Wong, MD, said NIVOPOSTOP 'represents a potential new standard,' in his comments as discussant of the results at the meeting's Plenary Session.
As immunotherapy for head and neck cancers evolve, so must the approach to managing these patients, said Wong, who is director of the Center for Disease Prevention Research at the Medical College of Wisconsin in Milwaukee.
'In a world where neoadjuvant and adjuvant anti–PD-1 [programmed cell death 1] are options for patient care, a multidisciplinary tumor board discussion is optimal and should include individual patient and social factors, as well as consideration of individual tumor growth dynamic,' Wong said.
'The NIVOPOSTOP study presents a major turning point,' he added. 'However, we face many steep obstacles ahead of us, foremost among these the completion of ongoing studies.'
Study Design and Results
The study enrolled 680 patients aged 75 years or younger with HNSCC who had complete macroscopic surgical resection of stage III or IV cancer. Half the patients were either smokers or heavy smokers, and the most common tumor site was the oral cavity. About 80% of patients had either stage IVA or IVB disease.
After surgical resection, patients were randomized to one of the two regimens. The treatment group received one dose of 240 mg nivolumab, followed by a dose of 360 mg nivolumab every 3 weeks plus standard-of-care 100 mg/m2 cisplatin every 3 weeks and 66 grays (Gy) of intensity-modulated RT (IMRT), followed by six doses of 480 mg nivolumab over 4 weeks. The control group received 100 mg/m2 cisplatin every 3 weeks and IMRT 66 Gy.
The rate of 3-year disease-free survival in the nivolumab plus CRT group was 63.1% vs 52.5% in the control group ( P = .034), representing a 24% improvement, Bourhis said.
The nivolumab plus CRT group also had a 37% reduced risk for cumulative incidence of locoregional relapses alone at 3 years, he added.
Compliance rates were similar between both groups. For example, RT compliance rates over 55 days were 95% for nivolumab plus CRT and 97% for CRT.
The proportion of patients experiencing more serious side effects in the 100 days following treatment was higher in the nivolumab plus CRT group than in the control group (13.1% vs 5.6%). The most common grade 4 adverse events in both groups were neutropenia and lymphocytopenia. Most treatment-related adverse events were less serious grade 1 or 2 events and were related to chemoradiotherapy in both groups. The nivolumab group had 'a slight increase' in renal toxicity (24% vs 15%) and 'a more pronounced increase' in thyroid disorders (20% vs 2%), Bourhis said.
Evidence Is Growing
NIVOPOSTOP adds to a body of evidence supporting the use of adjuvant immunotherapy in difficult-to-treat disease, Glenn Hanna, MD, director of the Center for Cancer Therapeutic Innovation at Dana-Farber Cancer Institute in Boston, said at the press conference. He cited results from the KEYNOTE-689 trial, reported in April at American Association for Cancer Research Annual Meeting 2025, in which patients with HNSCC were given perioperative neoadjuvant pembrolizumab followed by adjuvant pembrolizumab.
'It brings us into a space where we were with kidney cancers and with melanoma, to say what is the right sequence of immunotherapy?' Hanna said. He noted that NIVOPOSTOP and KEYNOTE-689 both reported similar outcomes.
'So do you give the immunotherapy first, or do we wait and do it in the adjuvant setting?' he said. Based on Bourhis' research, 'they are comparable.'
He added, 'I think now immunotherapy will be here and present for our head and neck patients undergoing cancer resection.'
NIVOPOSTOP received support from Bristol Myers Squibb and GORTEC. Bourhis reported having financial relationships with AstraZeneca, Bristol Myers Squibb, Merck Serono, and Merck Sharpe and Dohme.
Hanna reported having relationships with Actuate Therapeutics, Bicara Therapeutics, Boxer Capital, Bristol Myers Squibb, Coherus BioSciences, Elevar Therapeutics, Genentech, Greywolf Therapeutics, ImmunityBio, InhibRx, KSQ Therapeutics, Kura Oncology, Merck, Naveris, Nextech Invest, PDS Biotechnology, Regeneron, Remix Therapeutics, Replimune, Secura Bio, and Surface Oncology. Wong reported receiving research funding from Hookipa Pharma, Merck, and Novartis.