近日，中山大学马骏团队研究了不同时使用顺铂的Toripalimab联合治疗鼻咽癌的疗效与安全性。2025年8月21日出版的《美国医学会杂志》发表了这项成果。

使用程序性细胞死亡蛋白1（PD-1）阻断剂toripalimab，在不影响生存的情况下，省略高毒性的顺铂可能对鼻咽癌（NPC）是可行的。

为了评估在不同时使用顺铂的情况下，将toripalimab纳入诱导化疗和放疗治疗局部晚期鼻咽癌的疗效和安全性，2021年8月至2022年7月，研究组在中国13家医院进行了一项开放标签、多中心、随机3期临床试验，纳入532例T4N1M0或T1-4N2-3M0鼻咽癌患者；每个方案中有400例（75.2%）完成了试验。最后的随访日期是2025年3月21日。患者被随机分配到标准治疗组（n = 266)，接受toripalimab联合吉西他滨顺铂诱导化疗和同步顺铂放疗（100mg/m2，每周三次，共2个周期），或同时接受顺铂保留组（n = 266)，接受相同的方案，不同时使用顺铂。17个周期的toripalimab（每周三次240mg）分别分布在诱导、放疗和辅助阶段，分别为3、3和11个周期。主要终点为无失败生存期（非劣效裕度，8%）和所有级别呕吐的发生率（优势设计）。次要终点包括总生存期、局部无复发生存期、远处无转移生存期、安全性、肿瘤反应、生活质量和耐受性。

在意向治疗人群中的532名患者中（中位[IQR]年龄，47[39-54]岁；25.2%为女性），在中位随访37.0（范围，4.0-50.0）个月后，同时保留顺铂组的3年无失败生存率为88.3%，而标准治疗组为87.6%，差异为0.7%（单侧95%CI下限，-3.9%；P = .002 非劣效性；分层危险比，0.92[95%CI，0.66-1.79]；对数秩P = .73)。在安全性分析中，与标准治疗组相比，同时保留顺铂组的各级呕吐发生率显著降低（26.2%[68/260]对59.8%[156/261]；差异为33.6%[单侧95%CI，26.9%-∞]；P < .001). 患者报告的生活质量（参与率87.5%）和耐受性（参与率94.7%）在同时保留顺铂组中更好，主要是在胃肠道、功能和整体健康状况方面。

研究结果表明，在这项3期随机临床试验中，在局部晚期鼻咽癌患者中，不同时使用顺铂的toripalimab联合治疗是一种可行的治疗方法，具有无失败生存率高、毒性低的特点。

附：英文原文

Title: Toripalimab Combination Therapy Without Concurrent Cisplatin for Nasopharyngeal Carcinoma: The DIAMOND Randomized Clinical Trial

Author: The DIAMOND Study Group, Cheng Xu, Xiao-Yu Liang, Xin-Qiong Huang, Feng Jin, Kun-Yu Yang, Guang-Yuan Hu, Xiao-Dong Zhu, Ying Wang, Ying Huang, Ning Zhang, De-Sheng Hu, Ling Guo, Guo-Rong Zou, Xiao-Zhong Chen, Shao-Wen Xiao, Jin-Gao Li, Liang-Fang Shen, Yuan-Yuan Li, Jing Huang, Guo-Xian Long, Ling Li, Luo Huang, Long-Jiang She, Yuan Wu, Wei-Hua Zeng, Meng-Yun Qiang, Wei-Xin Liu, Yong Su, Ling-Long Tang, Fang-Yun Xie, Fei Han, Li-Xia Lu, Yan-Qun Xiang, Yan-Ping Mao, Wen-Fei Li, Xu Liu, Qi Yang, Guan-Qun Zhou, Rui Guo, Pu-Yun Ouyang, Xiao-Hui Wang, Lei Chen, Li-Ting Liu, Li Lin, Ji-Bin Li, Ai-Hua Lin, Hong-Yun Zhao, Shu-Bin Hong, Yu-Sheng Jie, Hui-Ling Huang, Xu-Hua Tang, Yue-Can Zeng, Jing-Ping Yun, Sheng-Bing Zang, Zi-Ming Du, Zu-Lu Ye, Li-Zhi Liu, Li Tian, Hao-Jiang Li, Ying-Lin Peng, Na Liu, Ying-Qin Li, Ye-Lin Liang, Han-Miao Wei, Yu-Pei Chen, Yuan Zhang, Xiao-Jing Du, Jia-Wei Lv, Ying Sun, Jun Ma

Issue&Volume: 2025-08-21

Abstract:

Importance  With the programmed cell death protein 1 (PD-1) blockade toripalimab, omitting highly toxic concurrent cisplatin may be feasible for nasopharyngeal carcinoma (NPC) without compromising survival.

Objective  To evaluate the efficacy and safety of toripalimab incorporated into induction chemotherapy and radiotherapy, without concurrent cisplatin, for locoregionally advanced NPC.

Design, Setting, and Participants  Open-label, multicenter, randomized phase 3 clinical trial conducted from August 2021 to July 2022 at 13 hospitals in China, enrolling 532 patients with T4N1M0 or T1-4N2-3M0 NPC; 400 (75.2%) completed the trial per protocol. The final date of follow-up was March 21, 2025.

Interventions  Patients were randomly assigned to either the standard therapy group (n=266), receiving toripalimab with gemcitabine-cisplatin induction chemotherapy and concurrent cisplatin-radiotherapy (100 mg/m2 triweekly for 2 cycles), or the concurrent cisplatin–sparing group (n=266), receiving the same regimen without concurrent cisplatin. The 17 cycles of toripalimab (240 mg triweekly) were distributed across the induction, radiotherapy, and adjuvant phases as 3, 3, and 11 cycles, respectively.

Main Outcomes and Measures  Coprimary end points were failure-free survival (noninferiority margin, 8%) and incidence of all-grade vomiting (superiority design). Secondary end points included overall survival, locoregional recurrence-free survival, distant metastasis–free survival, safety, tumor response, quality of life, and tolerability.

Results  In the 532 patients in the intention-to-treat population (median [IQR] age, 47 [39-54] years; 25.2% women), after a median follow-up of 37.0 (range, 4.0-50.0) months, the concurrent cisplatin–sparing group had a 3-year failure-free survival rate of 88.3% vs 87.6% in the standard therapy group, a difference of 0.7% (lower limit of the 1-sided 95% CI, 3.9%; P=.002 for noninferiority; stratified hazard ratio, 0.92 [95% CI, 0.66-1.79]; log-rank P=.73). In the safety analysis, the incidence of all-grade vomiting was significantly lower in the concurrent cisplatin–sparing group vs the standard therapy group (26.2% [68/260] vs 59.8% [156/261]; difference, 33.6% [1-sided 95% CI, 26.9%-∞]; P<.001). Patient-reported quality of life (participation rate, 87.5%) and tolerability (participation rate, 94.7%) were better in the concurrent cisplatin–sparing group, primarily in gastrointestinal, functional, and global health status.

Conclusions and Relevance  In this phase 3 randomized clinical trial, among patients with locoregionally advanced NPC, toripalimab combination therapy without concurrent cisplatin was a feasible treatment with high efficacy in failure-free survival and low toxicity.

DOI: 10.1001/jama.2025.13205

Source: https://jamanetwork.com/journals/jama/fullarticle/2837950