Results from the international phase 3 NIVOPOSTOP clinical trial found that adding nivolumab to chemoradiotherapy after surgery can decrease the chance of recurrence in people with locally advanced head and neck squamous cell carcinoma (HNSCC).

This is one of the first studies of late to show an improvement in the standard of care for these patients in more than two decades. The research was presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

About half of people with locoregionally advanced HNSCC will have their cancer removed with surgery. After surgery, those at high risk for their cancer returning receive chemoradiotherapy; however, the cancer returns in up to 50% of patients who receive this treatment.

NIVOPOSTOP studied whether adding nivolumab to chemoradiotherapy after surgery could help delay the return of cancer in people with locoregionally advanced HNSCC at high risk of recurrence.

The study looked at data accrued until a prespecified time from 666 of the 680 enrolled patients. The study participants were younger than 75 and had locoregionally (local cancer with lymph node spread) advanced HNSCC.

The patients had to be identified as having a high risk of recurrence following surgery to participate in the study.

After surgery, the patients were randomly assigned to one of two treatment groups:

• Group A (334 patients) received chemoradiotherapy (66 total grays of radiation, along with the systemic chemotherapy drug cisplatin) every 3 weeks for 3 cycles. A gray is a unit of absorbed dose of radiation to a tumor.
• Group B (332 patients) received an initial dose of nivolumab followed by nivolumab in combination with chemoradiotherapy every 3 weeks for 3 cycles, then 6 cycles of nivolumab alone every 4 weeks.

Key Findings

At a median follow-up of 30.3 months, 252 of the 666 patients in the trial experienced a recurrence or had died. The researchers found that:

• The odds of disease-free survival were 24% higher in the patients who received nivolumab with chemoradiotherapy.
• In the patients who received nivolumab, 63.1% had no signs of cancer recurrence 3 years after treatment vs. 52.5% of patients who received chemoradiotherapy alone.

Nivolumab led to more serious side effects in patients. In the 100 days following treatment, 13.1% of patients who received nivolumab with chemoradiotherapy experienced a grade 4 adverse event vs. 5.6% of patients who received chemoradiotherapy alone. The most common grade 4 adverse events in both groups were neutropenia and lymphocytopenia.

“The outcome for patients with locoregionally advanced head and neck cancers remains generally poor, with only 50% to 55% of patients free of disease at 3 years when treated with the standard of care. There is clearly a need for more effective and also well-tolerated treatments. We have been trying for more than 20 years to improve this standard of care,” said lead study author Jean Bourhis, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland.

“Adjuvant nivolumab with chemoradiotherapy in resected high-risk head and neck squamous cell carcinoma improved disease-free survival regardless of tumor PD-L1 status. This is the first study to show the benefit of nivolumab added to chemoradiotherapy in head and neck squamous cell carcinoma,” said Glenn J. Hanna, MD, Director of the Center for Cancer Therapeutic Innovation at Dana-Farber Cancer Institute and an expert in head and neck cancers.

“As perioperative, meaning neoadjuvant and adjuvant pembrolizumab therapy recently showed improved outcomes in a similar population, there will be a focus on how to best sequence immunotherapy for these patients,” Hanna added.

The researchers plan to share updated overall survival data when the prespecified mortality numbers are reached, likely in 2026 or 2027.

Source: ASCO