According to results from the NIVOPOSTOP phase 3 trial, there is a statistically and clinically meaningful improvement in disease-free survival (DFS) with the addition of adjuvant nivolumab to standard cisplatin-based chemoradiotherapy (CRT) in patients with resected locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) at high risk of relapse.

These results will be presented by Jean Bourhis, MD, Bâtiment Hospitalier, Lausanne, Switzerland, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting at Chicago, Illinois.

More effective treatments for LA-SCCHN are needed as the current standard of care, adjuvant cisplatin-radiotherapy (CRT), frequently results in recurrence for patients. Researchers conducted a phase 3 trial to evaluate the efficacy of additional nivolumab to cisplatin-radiotherapy compared to cisplatin-radiotherapy alone.

This international, randomized, open-label study enrolled patients over the age of 75 years with ECOG performance status 0–1 and high-risk features following resection of oral cavity, oropharynx, hypopharynx, or laryngeal cancers. High-risk criteria included extracapsular extension, positive surgical margins, ≥4 involved lymph nodes, or extensive perineural invasion. Patients were randomized 1:1 to receive either standard adjuvant CRT alone (66 Gy RT and cisplatin 100 mg/m² Q3W × 3 cycles) or CRT combined with nivolumab (240 mg IV pre-CRT, followed by 360 mg Q3W × 3 during CRT, then 480 mg Q4W × 6 post-CRT).

The primary end point was DFS and secondary end points included overall survival (OS) and safety.

A total of 680 patients were randomized, with DFS analysis based on 666 patients (334 cisplatin-radiotherapy vs 332 nivolumab plus cisplatin-radiotherapy) and 252 DFS events at a median follow-up of 30.3 months. When compared to cisplatin-radiotherapy alone, DFS was significantly improved with nivolumab plus cisplatin-radiotherapy (hazard ratio, [HR], 0.76; 95% confidence interval [CI], 0.60 to 0.98; P = .034). The 3-year DFS was 63.1% (95% CI, 57.0 to 68.7%) in the nivolumab plus cisplatin-radiotherapy arm vs 52.5% (95% CI, 46.2 to 58.4%) in the cisplatin-radiotherapy alone arm.

In terms of safety, there were higher rates of grade 4 adverse events with nivolumab plus cisplatin-radiotherapy (13.1% vs 5.6%), though treatment-related deaths were similar (0.6% vs 0.7%).

"Adjuvant NIVO added to CRT after surgery provided a statistically and clinically meaningful DFS improvement in PD-L1 all-comers patients,” the researchers concluded. They added, “This is the first time in over 2 decades that a therapy demonstrated superiority over SOC CRT in patients with resected LA-SCCHN at high-risk of relapse.”

Source:

Bourhis J, Auperin A, Borel C, et al. NIVOPOSTOP (GORTEC 2018-01): A phase III randomized trial of adjuvant nivolumab added to radio-chemotherapy in patients with resected head and neck squamous cell carcinoma at high risk of relapse. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA2.