Breaking a 20-Year Standstill: Postoperative Nivolumab in Head and Neck Cancer

• Head and neck squamous cell carcinoma (HNSCC) imposes a substantial disease burden worldwide. At diagnosis, approximately 40–60% of these patients have surgically resectable disease.
• However, particularly for patients at high risk of recurrence (for example, with extracapsular spread or positive surgical margins), postoperative adjuvant (preventive) treatment has remained unchanged for many years: cisplatin given with radiotherapy (CRT).
• This approach has been the standard of care for the past 20 years, but it remains insufficient to prevent recurrence in many patients.
• Presented at ASCO 2025, NIVOPOSTOP revealed a striking development that could change this situation: adding the immunotherapy agent nivolumab to CRT significantly prolonged disease-free survival and reduced the risk of cancer recurrence by 24%.

NIVOPOSTOP Study Summary

• Full name: GORTEC 2018-01 / NIVOPOSTOP
• Design: Phase 3, randomized, open-label, multinational
• Participants:
  • 680 patients (surgically resected, locally advanced head and neck squamous cell carcinoma - HNSCC)
  • Age <75, ECOG 0-1
  • Primary tumors in the oral cavity, oropharynx, hypopharynx or larynx
  • Patients at high risk of recurrence: Extracapsular spread, positive surgical margins, ≥4 involved lymph nodes, multiple perineural invasion

Treatment Arms:

🅰️ Standard arm (CRT):

• 66 Gy IMRT + cisplatin 100 mg/m² Q3W (3 cycles)

🅱️ Experimental arm (NIVO + CRT):

• Nivolumab 240 mg (1 dose before CRT)
• NIVO 360 mg every 3 weeks during CRT (3 doses)
• Maintenance NIVO 480 mg every 4 weeks after CRT (6 doses)

Findings: A Breakthrough in Disease-Free Survival (DFS)

• Median follow-up: 30.3 months
• Primary endpoint: DFS – statistically and clinically significant improvement

🔎 This corresponds to a 24% reduction in recurrence risk .

Safety Data: A Notable Increase in Side Effects

• CRT arm: 5.6%
• NIVO + CRT arm: 13.1% (within 100 days); + 1.2% (up to 9 months)

Treatment-related deaths:

• NIVO + CRT: 0.6%
• CRT: 0.7%

👉 Although serious treatment-related side effects increased, no significant difference in death rates was observed.

Clinical and Practical Implications

🔬 For the first time in 20 years, a new combination has been developed that improves disease-free survival in postoperative adjuvant treatment.

🏥 These results were obtained in all patients, regardless of tumor PD-L1 expression.

🧪 Overall survival (OS) analyses are ongoing, but the DFS benefit alone appears sufficient to change practice.

Conclusion: Nivolumab Brings New Momentum to Adjuvant CRT

The NIVOPOSTOP study demonstrated that adding nivolumab to postoperative adjuvant treatment significantly reduced recurrence risk in patients with advanced head and neck SCC. These results appear likely to lead to changes in head and neck cancer guidelines in the coming period.