Head and neck cancers most often begin in the squamous cells lining the moist surfaces of the mouth, throat, and other areas within the head and neck region. For patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), about half undergo surgery to remove the tumor. Those at high risk of recurrence typically receive chemoradiotherapy afterward, yet up to 50% still experience a return of the disease. The NIVOPOSTOP trial marks one of the first meaningful improvements in the standard of care for this population in over two decades. The study investigated whether adding nivolumab to postoperative chemoradiotherapy could help delay or prevent cancer recurrence in patients with high-risk, locoregionally advanced HNSCC.

A total of 680 patients were randomized. Disease-free survival (DFS) analysis was conducted on 666 patients randomized before the cutoff date (334 in Arm A vs. 332 in Arm B; intent-to-treat analysis), with 252 events observed at a median follow-up of 30.3 months (interquartile range [IQR], 16.0–44.9). Baseline characteristics were balanced between the two arms. DFS was significantly improved across PD-L1 all-comers in the adjuvant nivolumab plus chemoradiotherapy arm compared to chemoradiotherapy alone. The 3-year DFS rate was 52.5% with chemoradiotherapy alone versus 63.1% with nivolumab plus chemoradiotherapy. Overall survival (OS) analysis will be conducted once the required number of deaths (283) is reached; currently, 158 deaths have occurred. Compliance with chemoradiotherapy was similar between arms. 

The safety analysis—conducted up to 9 months after chemoradiotherapy—included patients who received at least one dose of treatment. Grade 4 adverse events were less frequent with chemoradiotherapy alone compared to nivolumab plus chemoradiotherapy. Treatment-related deaths occurred in 0.7% and 0.6% of patients in the chemoradiotherapy and nivolumab plus chemoradiotherapy arms, respectively.

KOL insights: 

“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.” – Expert Opinion.

Conclusion:

In the evolving landscape of head and neck cancer treatment—where both neoadjuvant and adjuvant anti–PD-1 therapies are emerging options—a multidisciplinary tumor board discussion is essential. Treatment decisions should incorporate not only clinical factors, such as individual tumor growth dynamics, but also patient-specific and social considerations. 

NIVOPOSTOP trial demonstrated that the addition of adjuvant nivolumab to chemoradiotherapy following surgery significantly improved disease-free survival, regardless of tumor PD-L1 expression status. This represents the first therapeutic advance in over two decades to show superiority over standard-of-care cisplatin-based chemoradiotherapy in patients with resected locally advanced squamous cell carcinoma of the head and neck at high risk of relapse. The successful integration of immunotherapy earlier in the treatment course of head and neck squamous cell carcinoma signifies a long-awaited breakthrough in this setting. These findings have the potential to impact a broad population of patients with locally advanced disease, for whom the risk of recurrence remains high and effective treatment options have been limited.