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.

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.

NIVOPOST-OP试验旨在评估在这一背景下，通过纳武利尤单抗添加到顺铂和放疗中，对程序性死亡1受体阻断的疗效和安全性。

Methods

This open-label, phase 3 trial evaluated adding nivolumab to cisplatin and radiotherapy after surgery for LA-SCCHN with high-risk pathological features.

这项开放标签、III期临床试验评估了在手术后对具有高危病理特征的局部晚期头颈部鳞状细胞癌（LA-SCCHN）患者添加纳武利尤单抗至顺铂和放疗的治疗效果。

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.

主要纳入标准为年龄在19至74岁之间，东部肿瘤协作组（Eastern Cooperative Oncology Group）表现状态评分为0-1，口腔、口咽、喉或下咽的鳞状细胞癌已行宏观完整切除，且至少具有一个高危病理特征：淋巴结包膜外扩展、显微镜下切缘阳性、四个或更多颈部淋巴结受累但无包膜外扩展，以及多发性神经周围侵犯。在六个国家（法国、西班牙、波兰、比利时、希腊和瑞士）的82个研究地点共招募了680名参与者，按1:1的比例随机分配接受顺铂和放疗（66 Gy，顺铂100 mg/m2静脉注射，每3周一次，共三个周期）；或纳武利尤单抗240 mg静脉注射，随后进行顺铂和放疗，同时给予三个周期的联合纳武利尤单抗360 mg，每3周一次，以及六个周期的辅助纳武利尤单抗480 mg，每4周一次。

The primary endpoint was disease-free survival as per investigator assessment in the intention-to-treatpopulation. 230 disease-free survival events (relapses or deaths) were required to detect a hazard ratioof 0·65 with 0·05 two-sided α error, with 90% power.

主要终点是意向治疗人群中根据研究者评估的无病生存。需要230个无病生存事件（复发或死亡），以检测到0.65的风险比，双侧α错误为0.05，具有90%的统计功效。

The trial is registered at ClinicalTrials.gov (NCT03576417) and is active, but not recruiting.

该试验已在ClinicalTrials.gov注册（NCT03576417），目前正在进行中，但不再招募新患者。

Results

The 680 patients were recruited from Oct 15, 2018, to July 3, 2024.

这680名患者是从2018年10月15日至2024年7月3日招募的。

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).

分析基于666名随机分配的参与者，截至截止日期（2024年4月30日），此时所需事件数量已达到（中位随访期为30.3个月）。

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).

无病生存期通过使用纳武单抗、顺铂和放疗显著改善，与仅使用顺铂和放疗相比，无论程序性死亡配体1表达如何（HR 0·76; 95% 置信区间 0·60-0·98; 分层对数秩检验p值=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).

与仅使用顺铂和放疗相比，使用纳武单抗、顺铂和放疗的参与者中与治疗相关的4级不良事件的发生率有所增加（312人中有30人[10%]，而306人中有16人[5%]）。

Treatment-related deaths occurred in two participants in each group.

每组中有两名参与者发生了与治疗相关的死亡。

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.

在高风险可切除的局部晚期鳞状细胞头颈部癌（LA-SCCHN）患者中，尼伏单抗联合顺铂和放疗可适度增加毒性效应，同时改善无病生存期，可被提议作为新的标准治疗。

funding

Groupe Oncologie Radiotherapie Tete Et Cou (GORTEC) and Bristol Myers Squibb.

头颈肿瘤放射治疗肿瘤学组（GORTEC）和百时美施贵宝公司。