Adding the PD-1 inhibitor nivolumab to standard chemoradiotherapy after surgery significantly reduced recurrence rates for patients with locally advanced head and neck squamous cell carcinoma who are at high risk for recurrence, according to data presented at the 2025 ASCO Annual Meeting.1
At a median follow-up of 30.3 months, results from the phase III NIVOPOSTOP trial demonstrated a significant improvement in disease-free survival, from 52.5% in the control group to 63.1% among patients treated with nivolumab. Authors of the study emphasized that these findings provide compelling evidence supporting nivolumab as an adjuvant treatment, potentially establishing a new standard of care for patients with resected head and neck squamous cell carcinoma at high risk for recurrence.
Jean Bourhis, MD, PhD
“The outcome for patients with locoregionally advanced head and neck cancers remains generally poor,” said lead study author Jean Bourhis, MD, PhD, Chief Medical Doctor, Radiation Oncology, Lausanne University Hospital, Switzerland. “With the developments over the past decade, including this research, we can now consider updating this long-standing standard of care.”
Background and Study Details
Surgery followed by chemoradiotherapy has remained the standard of care for more than 20 years for patients at high risk for recurrence of head and neck cancer from features such as extracapsular extension and positive surgical margins. Despite this intensive treatment, he noted, recurrence rates approach 50%.
The NIVOPOSTOP trial enrolled 666 patients (< age 75) with surgically resected locally advanced head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients exhibited high-risk pathologic features predicting recurrence.
Participants were randomly assigned to two groups: one received standard chemoradiotherapy (daily radiation with cisplatin chemotherapy every 3 weeks for three cycles), and the other received chemoradiotherapy combined with nivolumab. The nivolumab regimen began with an initial dose before chemoradiotherapy, concurrent administration every 3 weeks during chemoradiotherapy, and continued with six additional nivolumab cycles every 4 weeks.
Improvement in Disease-Free Survival
At a median follow-up of 30.3 months, findings from the NIVOPOSTOP study showed a significant improvement in the primary endpoint of disease-free survival. The 3-year disease-free survival rate was 63.1% among patients treated with nivolumab vs 52.5% in the control group. The hazard ratio was 0.76, indicating a 24% reduction in recurrence risk (P = .003).
Of note, said Dr. Bourhis, the improved disease-free survival was primarily driven by enhanced locoregional control. A consistent benefit was observed across diverse patient subgroups, including variations in age, gender, tumor site, pathologic stage, and human papillomavirus (HPV) p16 status.
Dr. Bourhis emphasized that the improved outcomes came with a manageable increase in toxicity. Grade 4 adverse events, considered life-threatening, occurred in 13.1% of nivolumab-treated patients vs 5.6% of those receiving chemoradiotherapy alone. The most frequent severe toxicities included neutropenia and lymphocytopenia.
Clinical Implications
Additional considerations for clinical implementation include strategies for patient selection and biomarker validation. The NIVOPOSTOP trial did not specifically select patients based on PD-L1 expression, which warrants further exploration to identify individuals most likely to benefit from treatment. The role of biomarkers such as PD-L1 expression and HPV status in optimizing personalized treatment strategies also remains an area of ongoing research.
“Longer follow-up will be critical to confirm whether improvements in disease-free survival translate into meaningful overall survival benefits and further clarify the full benefit-risk profile of this promising new approach,” Dr. Bourhis concluded.
DISCLOSURE: Dr. Bourhis has served as a consultant or advisor to AstraZeneca, Bristol Myers Squibb, Merck Serono, and MSD. For full disclosures of the other study authors, visit coi.asco.org.
REFERENCE
1. Bourhis J, et al: 2025 ASCO Annual Meeting. Abstract LBA2.Presented June 2, 2025
EXPERT POINT OF VIEW
Invited discussant of the NIVOPOSTOP trial, Stuart J. Wong, MD, Professor of Medicine in Hematology Oncology and Director of the Head and Neck Cancer Program at the Medical College of Wisconsin, Milwaukee, underscored the transformative potential of the study’s findings.
Stuart J. Wong, MD
“Postoperative chemoradiation with nivolumab clearly improves disease-free survival for patients with resected, locally advanced head and neck cancer featuring high-risk pathologic indicators,” he said. “This represents a significant potential advancement in our treatment standards.”
Dr. Wong also emphasized the importance of a multidisciplinary, personalized approach when integrating immune checkpoint inhibitors such as nivolumab effectively into treatment strategies. “A personalized approach that considers not only tumor characteristics but also individual patient and social factors is crucial,” he commented. “Factors such as patient support systems, accessibility to care, and treatment tolerability must all be carefully considered during decision-making.”
What Next?
Highlighting additional areas of needed research, Dr. Wong called attention to ongoing studies designed to refine patient selection and enhance outcomes further. He remarked that providers must strive to identify better predictive biomarkers beyond PD-L1 expression, which will enable more effective, personalized treatments.
Finally, Dr. Wong highlighted the necessity of deeper mechanistic insights into how radiation and immunotherapy interact. “Understanding the biological mechanisms underpinning radiation and immune responses will be essential for improving patient outcomes,” he said. “Ultimately, our goal is to significantly enhance long-term survival and quality of life for patients with head and neck cancer.”
DISCLOSURE: Dr. Wong reported financial relationships with Hookipa Pharma, Merck, and Novartis.
