近日，瑞士沃杜瓦大学Jean Bourhis团队研究了对于复发风险较高的头颈部鳞状细胞癌患者，术后将纳武单抗添加到顺铂和放疗中，与单独使用顺铂和放疗相比的疗效。2025年12月22日，《柳叶刀》杂志发表了这一成果。

术后顺铂和放疗是高危局部晚期头颈部鳞状细胞癌（LA-SCCHN）切除后的标准治疗方案。NIVOPOST-OP试验旨在评估在这种情况下，纳武单抗加顺铂和放疗的程序性死亡1阻断的有效性和安全性。

这项开放标签的临床3期试验评估了在顺铂和手术后放疗联合纳武单抗治疗具有高危病理特征的LA-SCCHN的疗效。主要入选标准为年龄19-74岁，东部肿瘤合作组评分0-1，口腔、口咽、喉部或下咽鳞状细胞癌，经宏观完全切除，至少有一项高危病理特征：淋巴结囊外延伸、镜下边缘阳性、四个或更多宫颈淋巴结累及但无囊外延伸，以及多发性神经周围浸润。从6个国家（法国、西班牙、波兰、比利时、希腊和瑞士）的82个地点招募的680名参与者被随机按1:1分配接受顺铂和放疗（66 Gy，顺铂100mg/m²静脉注射，每3周一次，共3个周期）；或静脉注射纳武单抗240毫克，然后顺铂和放疗，同时服用纳武单抗360毫克每3周1次，6个周期辅助纳武单抗480毫克每4周1次。主要终点是研究者在意向治疗人群中评估的无病生存期。230例无病生存事件（复发或死亡）检测到的风险比为0.65，双侧α误差为0.05，功率为90%。

680例患者于2018年10月15日至2024年7月3日招募。该分析基于666名随机分配的参与者，直到截止日期（2024年4月30日），此时达到所需的事件数量（中位随访30.3个月）。与单用顺铂和放疗相比，纳武单抗、顺铂和放疗的无病生存率显著提高，且与程序性死亡配体1的表达无关（HR 0.76; 95% CI 0.60 - 0.98；分层对数秩检验p值= 0.034）。与顺铂和放疗相比，纳武单抗、顺铂和放疗的治疗相关4级不良事件发生率增加（312例中30例[10%]vs 306例中16例[5%]）。每组均有两名受试者出现治疗相关死亡。

研究结果表明，纳武单抗联合顺铂和放疗可提高高危切除LA-SCCHN的无病生存期，但毒性效应增加中等，可作为新的标准治疗方案提出。

附：英文原文

Title: 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

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

Issue&Volume: 2025-12-22

Abstract:

Background

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.

Methods

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.

Findings

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.

Interpretation

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.

DOI: 10.1016/S0140-6736(25)01850-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01850-1/abstract