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特瑞普利单抗或安慰剂加化疗作为晚期鼻咽癌一线治疗方案的3期试验
作者:小柯机器人 发布时间:2021/8/8 12:08:32

中山大学肿瘤中心徐瑞华团队完成特瑞普利单抗或安慰剂加化疗作为晚期鼻咽癌一线治疗方案的一项多中心随机3期试验。相关论文于2021年8月2日发表在《自然—医学》杂志上。

吉西他滨-顺铂(GP)化疗是复发或转移性鼻咽癌(RM-NPC)的标准一线系统疗法。在一项国际双盲3期试验中(ClinicalTrials.gov编号:NCT03581786),289名患有RM-NPC且之前未接受过复发或转移性疾病化疗的患者被随机分配(1/1)接受特瑞普利单抗(一种抗人类PD-1的单克隆抗体)或安慰剂,每3周与GP联合治疗,最多六个周期,之后接受特瑞普利单抗或安慰剂的单项治疗。主要终点是无进展生存期(PFS),由一个单盲独立的审查委员会根据RECIST v.1.1评估。在预先指定的中期PFS分析中,与安慰剂组相比,特瑞普利单抗组的PFS有明显改善:中位PFS为11.7个月对8.0个月,风险率(HR)=0.52(95%置信区间(CI):0.36-0.74),P=0.0003。在包括PD-L1表达在内的各关键亚组中,均观察到PFS的改善。

截至2021年2月18日,与安慰剂组相比,特瑞普利单抗组的死亡风险降低了40%(HR=0.603(95%CI:0.364-0.997))。两组之间≥3级不良事件(AE)(89.0%对89.5%)、导致特瑞普利单抗/安慰剂停药的AE(7.5&对4.9%)和致命AE(2.7%对2.8%)的发生率相似;然而,免疫相关AE(39.7%对18.9%)和≥3级输液反应(7.5%对0.7%)在特瑞普利单抗更为频繁。

总之,在GP化疗的基础上加用特瑞普利单抗作为RM-NPC患者的一线治疗方案,与单独使用GP相比,提供了更好的PFS,而且安全状况可控。

附:英文原文

Title: Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial

Author: Mai, Hai-Qiang, Chen, Qiu-Yan, Chen, Dongping, Hu, Chaosu, Yang, Kunyu, Wen, Jiyu, Li, Jingao, Shi, Ying-Rui, Jin, Feng, Xu, Ruilian, Pan, Jianji, Qu, Shenhong, Li, Ping, Hu, Chunhong, Liu, Yi-Chun, Jiang, Yi, He, Xia, Wang, Hung-Ming, Lim, Wan-Teck, Liao, Wangjun, He, Xiaohui, Chen, Xiaozhong, Liu, Zhigang, Yuan, Xianglin, Li, Qi, Lin, Xiaoyan, Jing, Shanghua, Chen, Yanju, Lu, Yin, Hsieh, Ching-Yun, Yang, Muh-Hwa, Yen, Chia-Jui, Samol, Jens, Feng, Hui, Yao, Sheng, Keegan, Patricia, Xu, Rui-Hua

Issue&Volume: 2021-08-02

Abstract: Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase3 trial (ClinicalTrials.gov identifier: NCT03581786), 289patients with RM-NPC and no previous chemotherapy for recurrent or metastatic disease were randomized (1/1) to receive either toripalimab, a monoclonal antibody against human programmed death-1 (PD-1), or placebo in combination with GP every 3weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee according to RECIST v.1.1. At the prespecified interim PFS analysis, a significant improvement in PFS was detected in the toripalimab arm compared to the placebo arm: median PFS of 11.7 versus 8.0months, hazard ratio (HR)=0.52 (95% confidence interval (CI): 0.36–0.74), P=0.0003. An improvement in PFS was observed across key subgroups, including PD-L1 expression. As of 18February 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR=0.603 (95% CI: 0.364–0.997)). The incidence of grade≥3 adverse events (AEs) (89.0 versus 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5 versus 4.9%) and fatal AEs (2.7 versus 2.8%) was similar between the two arms; however, immune-related AEs (39.7 versus 18.9%) and grade≥3 infusion reactions (7.5 versus 0.7%) were more frequent in the toripalimab arm. In conclusion, the addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS compared to GP alone, and with a manageable safety profile.

DOI: 10.1038/s41591-021-01444-0

Source: https://www.nature.com/articles/s41591-021-01444-0

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex