Journal Article

Nivolumab added to cisplatin and radiotherapy versus cisplatin and radiotherapy alone after surgery for people with squamous cell carcinoma of the head and neck at a high risk of relapse (GORTEC 2018-01 NIVOPOST-OP): a randomised, open-label, phase 3 trial

Ruiz, Elisabeth Perez, Thureau, Sebastien, Bosset, Matthieu, Mesia, Ricard, Modesto, Anouchka, N'Guyen, France, Plana, Maria, Psyrri, Amanda, Greilsamer, Charlotte, Tao, Yungan, Saada, Esma, Bruna, Antoine, Daste, Amaury, Temam, Stephane, Malard, Olivier, Lopez, Stephane, Lefebvre, Gautier, Borel, Christian, Bourhis, Jean, Henry, Stephanie, Calderon, Benoit, Geoffrois, Lionnel, Rutkowski, Tomasz, Vanbockstael, Julie, Kazmierska, Joanna, Johnson, Alison, Da Silva Motta, Antonio, Thariat, Juliette, Bozec, Laurence, Chapet, Sophie, Even, Caroline, Pointreau, Yoann, Buiret, Guillaume, Blanchard, Pierre, Sun, Xu Shan, Bert, Mahasti, Karamouza, Eleni, Racadot, Severine, Sire, Christian, Bainaud, Matthieu, Aupérin, Anne, Cirauqui, Beatriz, Iruarrizaga, Eluska

2026

Overview

Postoperative cisplatin and radiotherapy is the standard of care for high-risk resected locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). The NIVOPOST-OP trial aimed to assess the efficacy and safety of programmed death 1 blockade by nivolumab added to cisplatin and radiotherapy in this setting. This open-label, phase 3 trial evaluated adding nivolumab to cisplatin and radiotherapy after surgery for LA-SCCHN with high-risk pathological features. The main inclusion criteria were age 19–74 years, an Eastern Cooperative Oncology Group performance status 0–1, squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx resected with macroscopic complete resection, and at least one high-risk pathological feature: nodal extracapsular extension, microscopically positive margins, four or more cervical nodal involvements without extracapsular extension, and multiple perineural invasions. 680 participants recruited in 82 sites across six countries (France, Spain, Poland, Belgium, Greece, and Switzerland) were randomly assigned 1:1 to receive cisplatin and radiotherapy (66 Gy, cisplatin 100 mg/m2 intravenously once every 3 weeks, for three cycles); or nivolumab 240 mg intravenously, followed by cisplatin and radiotherapy with three cycles of concomitant nivolumab 360 mg once every 3 weeks, and six cycles of adjuvant nivolumab 480 mg once every 4 weeks. The primary endpoint was disease-free survival as per investigator assessment in the intention-to-treat population. 230 disease-free survival events (relapses or deaths) were required to detect a hazard ratio of 0·65 with 0·05 two-sided α error, with 90% power. The trial is registered at ClinicalTrials.gov (NCT03576417) and is active, but not recruiting. The 680 patients were recruited from Oct 15, 2018, to July 3, 2024. The analysis was based on 666 participants randomly assigned until the cutoff date (April 30, 2024), at which point the required number of events was reached (median follow-up 30·3 months). Disease-free survival was significantly improved with nivolumab, cisplatin, and radiotherapy versus cisplatin and radiotherapy alone, irrespective of programmed death ligand 1 expression (HR 0·76; 95% CI 0·60–0·98; stratified log-rank test p value=0·034). There was an increase in the rate of participants with treatment-related grade 4 adverse events with nivolumab, cisplatin, and radiotherapy compared with cisplatin and radiotherapy (30 [10%] of 312 vs 16 [5%] of 306). Treatment-related deaths occurred in two participants in each group. Nivolumab added to cisplatin and radiotherapy in high-risk resected LA-SCCHN improves disease-free survival with moderate toxic effect increase, and can be proposed as a new standard treatment. Groupe Oncologie Radiotherapie Tete Et Cou (GORTEC) and Bristol Myers Squibb.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Aged / Antineoplastic Agents, Immunological / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Apoptosis / Cancer therapies / Chemotherapy / Cisplatin / Cisplatin - administration & dosage / Cisplatin - adverse effects / Cisplatin - therapeutic use / Fatalities / Female / Head and neck carcinoma / Head and Neck Neoplasms - mortality / Head and Neck Neoplasms - therapy / Humans / Hypopharynx / Immunotherapy / Internal Medicine / Labels / Larynx / Male / Metastasis / Middle Aged / Neck / Neoplasm Recurrence, Local / Nivolumab - administration & dosage / Nivolumab - adverse effects / Nivolumab - therapeutic use / Oncology / Oral carcinoma / Oral cavity / Oropharynx / Radiation therapy / Rank tests / Risk / Squamous cell carcinoma / Squamous Cell Carcinoma of Head and Neck - drug therapy / Squamous Cell Carcinoma of Head and Neck - mortality / Squamous Cell Carcinoma of Head and Neck - pathology / Squamous Cell Carcinoma of Head and Neck - surgery / Squamous Cell Carcinoma of Head and Neck - therapy / Standard of care / Surgery / Survival / Young Adult