In a phase III trial (GORTEC 2018-01, NIVOPOST-OP) reported in The Lancet, Bourhis et al found that the addition of adjuvant nivolumab to cisplatin and radiotherapy improved disease-free survival in patients with high-risk, resected, locally advanced squamous cell carcinoma of the head and neck (HNSCC).
Study Details
The open-label trial included 666 patients from sites in France, Spain, Poland, Belgium, Greece, and Switzerland. They were randomly assigned between October 2018 and July 2024 to receive radiotherapy at 66 Gy and cisplatin at 100 mg/m² every 3 weeks for three cycles without (n = 334) or with (n = 332) three cycles of concomitant nivolumab at 360 mg every 3 weeks followed by six cycles of nivolumab at 480 mg every 4 weeks. PD-L1 combined positive scores in the nivolumab group vs the control group were < 1 in 11% vs 14% of patients, 1 to 19 in 46% vs 50%, and 20 or greater in 43% vs 36%. The primary endpoint of the trial was investigator-assessed disease-free survival.
Key Findings
Median follow-up at the cutoff date (end of April 2024), when the required number of disease-free survival events for analysis was reached, was 30.3 months (interquartile range = 16.0–44.9 months).
Disease-free survival events occurred in 112 patients in the nivolumab group vs 140 patients in the control group (stratified hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.60–0.98, P = .034). Disease-free survival at 3 years was 63.1% (95% CI = 57.0–68.7%) vs 52.5% (95% CI = 46.2%–58.4%).
Stratified hazard ratios for disease-free survival according to PD-L1 combined positive score were 0.85 (95% CI = 0.42–1.75) for < 1, 0.64 (95% CI = 0.45–0.91) for 1 to 19, and 0.88 (95% CI = 0.56–1.37) for 20 or greater.
Treatment-related grade 3 adverse events occurred in 73% of patients in the nivolumab group vs 68% of the control group; treatment-related grade 4 events occurred in 10% vs 5%; and treatment-related serious adverse events occurred in 33% vs 19% of patients. Treatment-related deaths occurred in two patients in the nivolumab group (due to acute kidney injury and pancytopenia in one and aspiration pneumonia in one) and in two patients in the control group (due to acute respiratory syndrome, kidney injury, and sepsis in one and infection in one).
The investigators concluded: “Nivolumab added to cisplatin and radiotherapy in high-risk resected [locally advanced HNSCC] improves disease-free survival with moderate toxic effect increase, and can be proposed as a new standard treatment.”
Jean Bourhis, MD, of the Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Groupe Oncologie Radiotherapie Tete Et Cou (GORTEC) and Bristol Myers Squibb. For full disclosures of the study authors, visit thelancet.com.
