Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309)

被引：133

作者：

Yang, Yunpeng ^{[1
]}

Pan, Jianji ^{[2
]}

Wang, Hui ^{[3
]}

Zhao, Yuanyuan ^{[1
]}

Qu, Shenhong ^{[4
]}

Chen, Nianyong ^{[5
,6
]}

Chen, Xiaozhong ^{[7
]}

Sun, Yan ^{[8
]}

He, Xiaohui ^{[9
]}

Hu, Chaosu ^{[10
]}

Lin, Lizhu ^{[11
]}

Yu, Qitao ^{[12
]}

Wang, Siyang ^{[13
]}

Wang, Guihua ^{[14
]}

Lei, Feng ^{[15
]}

Wen, Jiyu ^{[16
]}

Yang, Kunyu ^{[17
]}

Lin, Zhixiong ^{[18
]}

Guo, Ye ^{[19
]}

Chen, Shaoqing ^{[20
]}

Huang, Xiaoming ^{[21
]}

Wu, Yanjie ^{[22
]}

Liang, Liang ^{[23
]}

Chen, Chenqi ^{[22
]}

Bai, Fan ^{[22
]}

Ma, Xiaopeng ^{[24
]}

Zhang, Yun ^{[23
]}

Leaw, Shiangjiin ^{[22
]}

Zhang, Li ^{[1
]}

Fang, Wenfeng ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Med Oncol Sun Yat, State Key Lab Oncol South China,Canc Ctr,Guangdong, 16th Floor,2 Bldg,Dongfeng East Rd, Guangzhou 510060, Guangdong, Peoples R China

[2] Fujian Canc Hosp, Dept Head & Neck Radiat Oncol, 420 Fuma Rd, Fuzhou 350014, Fujian, Peoples R China

[3] Hunan Canc Hosp, Thorac Radiotherapy Dept 1, 283 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China

[4] Guangxi Acad Med Sci, Peoples Hosp Guangxi Zhuang Autonomous Reg, Canc Res Inst, Otolaryngol Dept, 6 Tao Yuan Rd, Nanning 530021, Guangxi, Peoples R China

[5] Sichuan Univ, West China Hosp, Canc Ctr, Dept Head & Neck Oncol, 37 Guoxuexiang, Chengdu 610041, Sichuan, Peoples R China

[6] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, 37 Guoxuexiang, Chengdu 610041, Sichuan, Peoples R China

[7] Zhejiang Canc Hosp, Dept Head & Neck Radiotherapy, 38 Guangji Rd, Hangzhou 310022, Zhejiang, Peoples R China

[8] Beijing Canc Hosp, Radiotherapy Dept, 52 Fucheng Rd, Beijing 100142, Peoples R China

[9] Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, 17 Panjiayuannanli, Beijing 100021, Peoples R China

[10] Fudan Univ, Shanghai Canc Ctr, Dept Radiat, 270 Dongan Rd, Shanghai 200032, Peoples R China

[11] Guangzhou Tradit Chinese Med Univ, Affiliated Hosp 1, Dept Oncol, 16 Airport Rd, Guangzhou 510405, Guangdong, Peoples R China

[12] Guangxi Med Univ, Affiliated Canc Hosp, Dept Med Oncol Resp, 71 Hedi Rd, Nanning 530021, Guangxi, Peoples R China

[13] Sun Yat Sen Univ, Affiliated Hosp 5, Head & Neck Oncol Sect 1, 52 Meihua East Rd, Zhuhai 519000, Peoples R China

[14] Changsha Cent Hosp, Dept Oncol, 161 Shaoshan South Rd, Changsha 410004, Hunan, Peoples R China

[15] Peoples Hosp Zhongshan City, Head & Neck Radiotherapy Dept, 2 Sunwen East Rd, Zhongshan 528403, Guangdong, Peoples R China

[16] Guangdong Med Univ, Affiliated Hosp, Canc Ctr, Nasopharyngeal Canc Dis Ctr, 57 South Renmin Rd, Zhanjiang 524000, Guangdong, Peoples R China

[17] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Canc Ctr, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China

[18] Shantou Univ, Canc Hosp, Med Coll, Dept Radiat, 7 Raoping Rd, Shantou 515031, Guangdong, Peoples R China

[19] Tongji Univ, Shanghai East Hosp, Sch Med, Dept Oncol, 1800 Yuntai Rd, Shanghai 200123, Peoples R China

[20] Nanchang Univ, Affiliated Hosp 1, Dept Oncol, 17 Yongwaizheng St, Nanchang 330006, Jiangxi, Peoples R China

[21] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Otolaryngol Head & Neck Surg, 107 Yan Jiang West Rd, Guangzhou 510120, Guangdong, Peoples R China

[22] BeiGene Shanghai Co Ltd, Jing Kerry Ctr, Clin Dev, 20-F,Tower 3,1228 Middle Yanan Rd, Shanghai 200040, Peoples R China

[23] BeiGene Beijing Co Ltd, Clin Biomarker Sci & CDx Dev, 6 Jianguomenwai Ave,SK Tower,36th Floor, Beijing 100022, Peoples R China

[24] BeiGene Beijing Co Ltd, Bioinformat, 30 Sci Pk Rd,Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China

来源：

CANCER CELL | 2023年 / 41卷 / 06期

关键词：

biomarker; clinical trial; double-blinded; gene expression profiling; immunotherapy; nasopharyngeal carcinoma; PD-1; inhibitor; randomized; tislelizumab;

D O I：

10.1016/j.ccell.2023.04.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Checkpoint inhibitors are effective in recurrent/metastatic nasopharyngeal cancer (R/M NPC). RATIONALE-309 (NCT03924986) randomized 263 treatment-naive R/M NPC patients to tislelizumab or placebo every 3 weeks (Q3W), plus chemotherapy (Q3W for 4-6 cycles). At interim analysis, progression-free survival (PFS) was significantly longer with tislelizumab-chemotherapy versus placebo -chemotherapy (hazard ratio: 0.52; 95% confidence interval: 0.38, 0.73; p < 0.0001). PFS benefit for tislelizumabchemotherapy versus placebo-chemotherapy was observed regardless of programmed death-ligand 1 expression. PFS after next line of treatment and overall survival showed favorable trends for tislelizumab-chemotherapy versus placebo-chemotherapy. The safety profile was similar between arms. Gene expression profiling (GEP) identified immunologically "hot"tumors, and showed an activated dendritic cell (DC) signature was associated with tislelizumab-chemotherapy PFS benefit. Our results support that tislelizumab-chemotherapy should be considered as first-line treatment for R/M NPC, and GEP and activated DC signature results may help identify patients who might benefit most from immunochemotherapy treatment.

引用

页码：1061 / +

页数：17

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