本文由小咖机器人翻译整理

期刊来源：Lancet

原文链接：https://doi.org/10.1016/S0140-6736(24)00594-4

摘要内容如下：

背景

对于复发或转移性鼻咽癌，抗PD-1治疗和化疗是推荐的一线治疗，但PD-1阻断剂在局部晚期鼻咽癌患者中的作用尚不清楚。我们评估了PD-1抑制剂Sintilimab在该患者人群的标准放化疗中的应用。

方法

这项多中心、开放标签、平行组、随机、对照的3期临床试验在中国的9家医院进行。18-65岁新诊断的高危非转移性III-IVA期局部区域晚期鼻咽癌（不包括T3-4N0和T3N1）符合入选标准。患者被随机分配（1:1）接受吉西他滨和顺铂诱导化疗，随后接受顺铂同步放疗（标准治疗组）或每3周一次静脉注射200mg sintilimab的标准治疗12个周期（包括3个诱导周期、3个同步周期和6个辅助放疗周期；Sintilimab集团）。主要终点是从随机化到疾病复发（局部或远处）的无事件生存率或意向治疗人群中任何原因导致的死亡。次要终点包括不良事件。该试验已在ClinicalTrials.gov（NCT03700476）注册，现已完成。后续行动正在进行中。

调查结果

在2018年12月21日至2020年3月31日期间，425名患者入选并被随机分配到Sintilimab治疗组（n=210）或标准治疗组（n=215）。中位随访时间为41.9个月（IQR 38.0-44.8；主要数据截止期[2023年2月28日]有389例存活，366例[94%]至少随访36个月），Sintilimab治疗组的无事件生存率高于标准治疗组（36个月生存率86%[95%CI 81-90]vs 76%[70-81]；分层危险比为0.59[0.38~0.92]；P=0.019）。3-4级不良事件在Sintilimab组为155例（74%），标准治疗组为140例（65%），最常见的是口腔炎（68[33%]vs 64[30%]）、白细胞减少症（54[26%]vs 48[22%]）和中性粒细胞减少症（50[24%]vs 46[21%]）。Sintilimab治疗组有2例（1%）患者死亡（均被认为与免疫相关），标准治疗组有1例（<1%）患者死亡。Sintilimab组中有20例（10%）患者发生3-4级免疫相关不良事件。

解释

在放化疗中加入Sintilimab可改善无事件生存率，尽管不良事件较高但可控。有必要进行更长时间的随访，以确定该方案是否可作为高危局部晚期鼻咽癌患者的标准治疗方案。

翻译

摘要的中文译文见补充材料部分。

英文原文如下：

Abstracts

BACKGROUND  Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population.

METHODS  This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing.

FINDINGS  Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group.

INTERPRETATION  Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma.

TRANSLATION  For the Chinese translation of the abstract see Supplementary Materials section.

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