Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial

Zi-Xian Wang; Chengxu Cui; Jun Yao; Yanqiao Zhang; Mengxia Li; Jifeng Feng; Shujun Yang; Yun Fan; Jianhua Shi; Xizhi Zhang; Lin Shen; Yongqian Shu; Cailian Wang; Tianyang Dai; Teng Mao; Long Chen; Zengqing Guo; Bo Liu; Hongming Pan; Shundong Cang; Yi Jiang; Junye Wang; Min Ye; Zhendong Chen; Da Jiang; Qin Lin; Wei Ren; Junsheng Wang; Lin Wu; Yong Xu; Zhanhui Miao; Meili Sun; Conghua Xie; Ying Liu; Qifeng Wang; Lina Zhao; Qi Li; Canhong Huang; Ke Jiang; Kunyu Yang; Daojun Li; Yunpeng Liu; Zhitu Zhu; Rixin Chen; Liqun Jia; Wei Li; Wangjun Liao; Hong-Xu Liu; Daiyuan Ma; Jie Ma; Yanru Qin; Zhihong Shi; Qichun Wei; Ke Xiao; Yan Zhang; Ying Zhang; Xin Chen; Guanghai Dai; Jianxing He; Junhe Li; Guanghui Li; Yong Liu; Zhihua Liu; Xianglin Yuan; Junping Zhang; Zhichao Fu; Yifu He; Fang Ju; Zheng Liu; Peng Tang; Tiejun Wang; Weibo Wang; Jing Zhang; Xianming Luo; Xiongwen Tang; Rena May; Hui Feng; Sheng Yao; Patricia Keegan; Rui-Hua Xu; Feng Wang

doi:10.1016/j.ccell.2022.02.007

Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial

Cancer Cell. 2022 Mar 14;40(3):277-288.e3. doi: 10.1016/j.ccell.2022.02.007. Epub 2022 Mar 3.

Authors

Zi-Xian Wang¹, Chengxu Cui², Jun Yao³, Yanqiao Zhang⁴, Mengxia Li⁵, Jifeng Feng⁶, Shujun Yang⁷, Yun Fan⁸, Jianhua Shi⁹, Xizhi Zhang¹⁰, Lin Shen¹¹, Yongqian Shu¹², Cailian Wang¹³, Tianyang Dai¹⁴, Teng Mao¹⁵, Long Chen¹⁶, Zengqing Guo¹⁷, Bo Liu¹⁸, Hongming Pan¹⁹, Shundong Cang²⁰, Yi Jiang²¹, Junye Wang²², Min Ye²³, Zhendong Chen²⁴, Da Jiang²⁵, Qin Lin²⁶, Wei Ren²⁷, Junsheng Wang²⁸, Lin Wu²⁹, Yong Xu³⁰, Zhanhui Miao³¹, Meili Sun³², Conghua Xie³³, Ying Liu³⁴, Qifeng Wang³⁵, Lina Zhao³⁶, Qi Li³⁷, Canhong Huang³⁸, Ke Jiang³⁹, Kunyu Yang³⁹, Daojun Li⁴⁰, Yunpeng Liu⁴¹, Zhitu Zhu⁴², Rixin Chen⁴³, Liqun Jia⁴⁴, Wei Li⁴⁵, Wangjun Liao⁴⁶, Hong-Xu Liu⁴⁷, Daiyuan Ma⁴⁸, Jie Ma⁴⁹, Yanru Qin⁵⁰, Zhihong Shi⁵¹, Qichun Wei⁵², Ke Xiao⁵³, Yan Zhang⁵⁴, Ying Zhang⁵⁵, Xin Chen⁵⁶, Guanghai Dai⁵⁷, Jianxing He⁵⁸, Junhe Li⁵⁹, Guanghui Li⁶⁰, Yong Liu⁶¹, Zhihua Liu⁶², Xianglin Yuan⁶³, Junping Zhang⁶⁴, Zhichao Fu⁶⁵, Yifu He⁶⁶, Fang Ju⁶⁷, Zheng Liu⁶⁸, Peng Tang⁶⁹, Tiejun Wang⁷⁰, Weibo Wang⁷¹, Jing Zhang⁷², Xianming Luo⁷³, Xiongwen Tang⁷⁴, Rena May⁷⁵, Hui Feng⁷⁴, Sheng Yao⁷⁴, Patricia Keegan⁷⁵, Rui-Hua Xu⁷⁶, Feng Wang⁷⁷

Affiliations

¹ Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China.
² Cancer Hospital Chinese Academy of Medical Sciences, Beijing 100021, China.
³ The First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471000, China.
⁴ Harbin Medical University Cancer Hospital, Harbin 150081, China.
⁵ Army Medical Center of PLA, Chongqing 400042, China.
⁶ Jiangsu Cancer Hospital, Nanjing 210009, China.
⁷ Henan Cancer Hospital & Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China.
⁸ Zhejiang Cancer Hospital, Hangzhou 310022, China.
⁹ Linyi Cancer Hospital, Linyi 276000, China.
¹⁰ The Northern Jiangsu People's Hospital, Yangzhou 225001, China.
¹¹ Beijing Cancer Hospital, Beijing 100142, China.
¹² Jiangsu Province Hospital, Nanjing 210029, China.
¹³ Zhongda Hospital Southeast University, Nanjing 210009, China.
¹⁴ The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
¹⁵ Shanghai Chest Hospital, Shanghai 200030, China.
¹⁶ Guangxi Medical University Affiliated Tumor Hospital, Nanning 530000, China.
¹⁷ Fujian Cancer Hospital, Fuzhou 350000, China.
¹⁸ Shandong Cancer Hospital, Jinan 250117, China.
¹⁹ Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
²⁰ Henan Provincial People's Hospital, Zhengzhou 450000, China.
²¹ The Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515000, China.
²² Affiliated Hospital of Jining Medical University, Jining 272000, China.
²³ Jiangmen Central Hospital, Jiangmen 529000, China.
²⁴ The Second Hospital of Anhui Medical University, Hefei 230000, China.
²⁵ The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China.
²⁶ The First Affiliated Hospital of Xiamen University, Xiamen 361000, China.
²⁷ Nanjing Drum Tower Hospital, Nanjing 530000, China.
²⁸ Anyang Cancer Hospital, Anyang 455000, China.
²⁹ Hunan Cancer Hospital, Changsha 410000, China.
³⁰ West China Hospital of Sichuan University, Chengdu 610000, China.
³¹ The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
³² Jinan Central Hospital, Jinan 250000, China.
³³ Zhongnan Hospital of Wuhan University, Wuhan 430000, China.
³⁴ Henan Cancer Hospital & Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450000, China.
³⁵ Sichuan Cancer Hospital, Chengdu 610000, China.
³⁶ Xijing Hospital, Xi'an 710000, China.
³⁷ Shanghai General Hospital, Shanghai 200000, China.
³⁸ Nantong Tumor Hospital, Nantong 226000, China.
³⁹ Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430000, China.
⁴⁰ Yichang Central People's Hospital, Yichang 443000, China.
⁴¹ The First Hospital of China Medical University, Shenyang 110000, China.
⁴² The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China.
⁴³ Liuzhou People's Hospital, Liuzhou 545000, China.
⁴⁴ China-Japan Friendship Hospital, Beijing 100000, China.
⁴⁵ The First Bethune Hospital of Jilin University, Changchun 130000, China.
⁴⁶ Nanfang Hospital Southern Medical University, Guangzhou 510000, China.
⁴⁷ Liaoning Cancer Hospital & Institute, Shenyang 110000, China.
⁴⁸ The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
⁴⁹ The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China.
⁵⁰ The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
⁵¹ Xinxiang First People's Hospital, Xinxiang 453000, China.
⁵² The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310000, China.
⁵³ The Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China.
⁵⁴ Shijiazhuang People's Hospital, Shijiazhuang 050000, China.
⁵⁵ Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
⁵⁶ The Second People's Hospital of Yibin, Yibin 644000, China.
⁵⁷ Chinese PLA General Hospital, Beijing 100000, China.
⁵⁸ The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.
⁵⁹ The First Affiliated Hospital of Nanchang University, Nanchang 330000, China.
⁶⁰ The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China.
⁶¹ Xuzhou Central Hospital, Xuzhou 221000, China.
⁶² Jiangxi Cancer Hospital, Nanchang 330000, China.
⁶³ Tongji Hospital Affiliated to Tongji Medical College, Wuhan 430000, China.
⁶⁴ Shanxi Bethune Hospital, Taiyuan 030000, China.
⁶⁵ The 900th Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army, Fuzhou 350000, China.
⁶⁶ Anhui Provincial Cancer Hospital, Hefei 230000, China.
⁶⁷ Qingdao Central Hospital, Qingdao 266000, China.
⁶⁸ HanDan Central Hospital, Handan 056000, China.
⁶⁹ Tianjin Medical University Cancer Institute & Hospital, Tianjin 300000, China.
⁷⁰ The Second Hospital of Jilin University, Changchun 130000, China.
⁷¹ Shandong Provincial Hospital, Jinan 250000, China.
⁷² HuBei Cancer Hospital, Wuhan 430000, China.
⁷³ Shanghai Junshi Biosciences, Shanghai 200126, China.
⁷⁴ Shanghai Junshi Biosciences, Shanghai 200126, China; TopAlliance Biosciences, Rockville, MD 20850, USA.
⁷⁵ TopAlliance Biosciences, Rockville, MD 20850, USA.
⁷⁶ Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China. Electronic address: [email protected].
⁷⁷ Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China. Electronic address: [email protected].

PMID: 35245446
DOI: 10.1016/j.ccell.2022.02.007

Abstract

Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naïve advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p < 0.0001). The prespecified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade ≥3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naïve, advanced ESCC, with a manageable safety profile.

Keywords: PD-1 inhibitor; advanced esophageal squamous cell carcinoma; double-blind; immunotherapy; multi-center; paclitaxel plus cisplatin; randomized study.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Esophageal Neoplasms* / drug therapy
Esophageal Squamous Cell Carcinoma* / drug therapy
Humans
Progression-Free Survival

Substances

Antibodies, Monoclonal, Humanized
toripalimab