medwireNews: Adding nivolumab to adjuvant chemoradiotherapy (CRT) significantly improves the disease-free survival (DFS) of patients with resected, locally advanced head and neck squamous cell carcinoma (HNSCC) at high risk for recurrence, show phase 3 trial data.
Presenting the NIVOPOSTOP findings at the 2025 ASCO Annual Meeting, Jean Bourhis (CHUV, Bâtiment Hospitalier, Lausanne, Switzerland) explained that for over 20 years, the standard of care for this patient population has been adjuvant cisplatin plus radiotherapy, but 40–45% of patients relapse despite treatment, “defining an unmet clinical need.”
The investigators therefore investigated the addition of nivolumab to adjuvant CRT, as PD-1 inhibitors have shown efficacy in the treatment of recurrent or metastatic HNSCC and been established as the standard of care in these settings, he told the audience in Chicago, Illinois, USA.
The open-label trial enrolled 666 patients (75–77% men; 48–54% current smokers) with SCC of the oral cavity, oropharynx, hypopharynx, or larynx with complete macroscopic resection, pathologic stage III or IV, and high-risk pathologic features (nodal extra capsular extension and/or positive tumor margins, ≥4 nodal involvements, or multiple peri-neural invasion).
At a median follow-up of 30.3 months, the estimated 3-year DFS rate was 63.1% for the 332 participants who were randomly assigned to receive nivolumab plus CRT, which involved one dose of nivolumab 240 mg, followed by three doses of nivolumab 360 mg every 3 weeks alongside three cycles of cisplatin 100 mg/m2 every 3 weeks plus 66 Gy of radiotherapy, and then six doses of nivolumab 480 mg every 4 weeks.
This rate was significantly higher than the 52.5% rate observed among their 334 counterparts who received CRT alone and translated to a significant hazard ratio (HR) for recurrence or death of 0.76 in favor of the PD-1 inhibitor.
Bourhis pointed out that the DFS benefit offered by the addition of nivolumab was primarily due to a reduction in locoregional recurrence, the HR for which was a significant 0.63 favoring nivolumab.
He also noted that although the overall survival data favored nivolumab plus CRT, formal testing was not possible at this stage as the prespecified number of deaths had not been reached at data cutoff and additional follow-up was needed.
Moving onto the safety results, the presenter reported that the incidence of treatment-related adverse events (TRAEs) occurring within 9 months of CRT was largely similar between the groups, except for “a slight increase in grade 4” events with the addition of nivolumab, at a rate of 9.3% versus 5.2% with CRT alone.
This increase “appeared manageable, and importantly, there was no increase in grade 5 toxicity,” he said.
The most common TRAEs in both groups were related to CRT and included stomatitis, radiation skin injury, dysphagia, nausea, and hematologic toxicities. There was a “slight” increase in renal AEs and “a more pronounced” increase in thyroid disorders in the nivolumab group, highlighted Bourhis.
The incidence of late TRAEs, that is, those occurring more than 9 months after CRT, was comparable between the nivolumab and control arms, with any-grade events observed in 33.3% and 30.6% of patients, respectively, and grade 3 events in 1.3% and 0.4%. There were no grade 4 or 5 TRAEs in either treatment group.
Bourhis concluded that postoperative nivolumab added to standard of care CRT improved patient outcomes for this population and “could be proposed as a new standard treatment,” for the first time in 2 decades.
Discussant Stuart Wong (Medical College of Wisconsin, Milwaukee, USA) said that “the NIVOPOSTOP study represents a major turning point,” but he drew attention to the recently reported results of the KEYNOTE 689 trial, which showed a significant improvement in event-free survival with the use of the PD-1 inhibitor pembrolizumab before and after surgery in patients with locally advanced HNSCC.
He continued: “In a world where neoadjuvant as well as adjuvant anti-PD-1 options are available for patient care, the multidisciplinary tumor board discussion is optimal, and should include individual patient and social factors as well as consideration of individual tumor growth dynamics.
“Certainly PD-L1 baseline testing will also be part of this decision-making discussion.”
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2025 ASCO Annual Meeting; Chicago, Illinois, USA: 30 May–3 June