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

Yunpeng Yang; Jianji Pan; Hui Wang; Yuanyuan Zhao; Shenhong Qu; Nianyong Chen; Xiaozhong Chen; Yan Sun; Xiaohui He; Chaosu Hu; Lizhu Lin; Qitao Yu; Siyang Wang; Guihua Wang; Feng Lei; Jiyu Wen; Kunyu Yang; Zhixiong Lin; Ye Guo; Shaoqing Chen; Xiaoming Huang; Yanjie Wu; Liang Liang; Chenqi Chen; Fan Bai; Xiaopeng Ma; Yun Zhang; Shiangjiin Leaw; Li Zhang; Wenfeng Fang

doi:10.1016/j.ccell.2023.04.014

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

Cancer Cell. 2023 Jun 12;41(6):1061-1072.e4. doi: 10.1016/j.ccell.2023.04.014. Epub 2023 May 18.

Authors

Yunpeng Yang¹, Jianji Pan², Hui Wang³, Yuanyuan Zhao¹, Shenhong Qu⁴, Nianyong Chen⁵, Xiaozhong Chen⁶, Yan Sun⁷, Xiaohui He⁸, Chaosu Hu⁹, Lizhu Lin¹⁰, Qitao Yu¹¹, Siyang Wang¹², Guihua Wang¹³, Feng Lei¹⁴, Jiyu Wen¹⁵, Kunyu Yang¹⁶, Zhixiong Lin¹⁷, Ye Guo¹⁸, Shaoqing Chen¹⁹, Xiaoming Huang²⁰, Yanjie Wu²¹, Liang Liang²², Chenqi Chen²¹, Fan Bai²¹, Xiaopeng Ma²³, Yun Zhang²², Shiangjiin Leaw²¹, Li Zhang²⁴, Wenfeng Fang²⁵

Affiliations

¹ Department of Medical Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 16th Floor, No. 2 Building, Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong 510060, China.
² Department of Head & Neck Radiation Oncology, Fujian Cancer Hospital, No. 420, Fuma Road, Jinan District, Fuzhou, Fujian 350014 China.
³ Thoracic Radiotherapy Department I, Hunan Cancer Hospital, No. 283, Tongzipo Road, Yuelu District, Changsha, Hunan 410013 China.
⁴ Otolaryngology Department of the People's Hospital of Guangxi Zhuang Autonomous Region, Cancer Research Institute of Guangxi Academy of Medical Sciences, No.6 Tao Yuan Road, Nan Ning, Guangxi 530021, China.
⁵ Department of Head and Neck Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37 Guoxuexiang, Wuhou District, Chengdu, Sichuan 610041, China.
⁶ Department of Head and Neck Radiotherapy, Zhejiang Cancer Hospital, 38 Guangji Road, Gongshu District, Hangzhou, Zhejiang 310022, China.
⁷ Radiotherapy Department, Beijing Cancer Hospital, No. 52 Fucheng Road, Haidian District, Beijing 100142, China.
⁸ Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing 100021, China.
⁹ Department of Radiation, Fudan University Shanghai Cancer Centre, No. 270, Dong'an Road, Xuhui District, Shanghai 200032, China.
¹⁰ Department of Oncology, the First Affiliated Hospital of Guangzhou Traditional Chinese Medicine University, No. 16 Airport Road, Baiyun District, Guangzhou, Guangdong 510405, China.
¹¹ Department of Medical Oncology of Respiratory, the Affiliated Cancer Hospital of Guangxi Medical University, No. 71 Hedi Road, Nanning, Guangxi 530021, China.
¹² Head and Neck Oncology Section One of The Fifth Affiliated Hospital Sun Yat-sen University, No. 52 Meihua East Road, Xiangzhou District, Zhuhai, Guangzhou Province 519000, China.
¹³ Department of Oncology, Changsha Central Hospital, No. 161, Shaoshan South Road, Changsha, Hunan 410004, China.
¹⁴ Head and Neck Radiotherapy Department, The People's Hospital of Zhongshan City, No. 2 Sunwen East Road, Zhongshan, Guangdong 528403, China.
¹⁵ Cancer Center, Nasopharyngeal Cancer Disease Center, Affiliated Hospital of Guangdong Medical University, No. 57 South Renmin Road, Zhanjiang, Guangdong 524000, China.
¹⁶ Cancer Centre, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei 430022, China.
¹⁷ Department of Radiation, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, Guangdong 515031, China.
¹⁸ Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, No. 1800, Yuntai Road, Shanghai 200123, China.
¹⁹ Department of Oncology, the First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi 330006, China.
²⁰ Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou, Guangdong 510120, China.
²¹ Clinical Development, BeiGene (Shanghai) Co., Ltd., Jing An Kerry Centre, 20/F, Tower 3, 1228 Middle Yan'an Road, Shanghai 200040, China.
²² Clinical Biomarker Science and CDx Development, BeiGene (Beijing) Co., Ltd., 6 Jianguomenwai Avenue, SK Tower, 36th Floor, Chaoyang District, Beijing 100022, China.
²³ Bioinformatics, BeiGene (Beijing) Co., Ltd. 30 Science Park Road, Zhongguancun Life Science Park, Changping District, Beijing 102206, China.
²⁴ Department of Medical Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 16th Floor, No. 2 Building, Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong 510060, China. Electronic address: zhangli@sysucc.org.cn.
²⁵ Department of Medical Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 16th Floor, No. 2 Building, Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong 510060, China. Electronic address: fangwf@sysucc.org.cn.

PMID: 37207654
DOI: 10.1016/j.ccell.2023.04.014

Abstract

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 tislelizumab-chemotherapy 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. VIDEO ABSTRACT.

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

Publication types

Video-Audio Media
Multicenter Study
Clinical Trial, Phase III
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Humans
Nasopharyngeal Neoplasms* / drug therapy
Nasopharyngeal Neoplasms* / genetics
Nasopharyngeal Neoplasms* / pathology
Neoplasm Recurrence, Local / drug therapy
Neoplasm Recurrence, Local / pathology
Progression-Free Survival

Substances

tislelizumab
Antibodies, Monoclonal, Humanized

Associated data

ClinicalTrials.gov/NCT03924986