Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.
Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase 3 trial (ClinicalTrials.gov identifier: NCT03581786), 289 patients 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 3 weeks 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 8.0 months, 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 18 February 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.
吉西他滨-顺铂 (GP) 化疗是复发性或转移性鼻咽癌 (RM-NPC) 的标准一线全身治疗。在这项国际、双盲、III 期试验（ClinicalTrials.gov 标识符：NCT03581786）中，289 名 RM-NPC 患者且无复发性或转移性疾病的既往化疗史，按 1/1 随机分配接受特瑞普利单抗（一种针对人程序性死亡受体-1（PD-1）的单克隆抗体）或安慰剂联合 GP 每 3 周给药，最多 6 个周期，随后用特瑞普利单抗或安慰剂单药治疗。主要终点是根据 RECIST v.1.1 由盲法独立审查委员会评估的无进展生存期 (PFS)。在预设的中期 PFS 分析中，与安慰剂组相比，特瑞普利单抗组的 PFS 显著改善：中位 PFS 为 11.7 个月与 8.0 个月，风险比（HR）为 0.52（95%置信区间（CI）：0.36-0.74），P=0.0003。在包括 PD-L1 表达在内的关键亚组中观察到 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））。特瑞普利单抗/安慰剂治疗相关的 3 级及以上不良事件（AE）发生率（89.0%与 89.5%）、导致特瑞普利单抗/安慰剂停药的 AE（7.5%与 4.9%）和致死性 AE（2.7%与 2.8%）相似；然而，特瑞普利单抗组免疫相关 AE（39.7%与 18.9%）和 3 级及以上输液反应（7.5%与 0.7%）更常见。总之，与单独使用 GP 化疗相比，特瑞普利单抗联合 GP 化疗作为 RM-NPC 患者的一线治疗可显著改善 PFS，且安全性可控。
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