PMID- 34341578
OWN - NLM
STAT- MEDLINE
DCOM- 20211008
LR  - 20221207
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 27
IP  - 9
DP  - 2021 Sep
TI  - Toripalimab or placebo plus chemotherapy as first-line treatment in advanced 
      nasopharyngeal carcinoma: a multicenter randomized phase 3 trial.
PG  - 1536-1543
LID - 10.1038/s41591-021-01444-0 [doi]
AB  - 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.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Mai, Hai-Qiang
AU  - Mai HQ
AD  - 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.
FAU - Chen, Qiu-Yan
AU  - Chen QY
AD  - 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.
FAU - Chen, Dongping
AU  - Chen D
AD  - Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 
      Guangzhou, China.
FAU - Hu, Chaosu
AU  - Hu C
AD  - Fudan University Cancer Center, Shanghai, China.
FAU - Yang, Kunyu
AU  - Yang K
AD  - Union Hospital Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Wen, Jiyu
AU  - Wen J
AD  - Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
FAU - Li, Jingao
AU  - Li J
AD  - Jiangxi Cancer Hospital, Nanchang, China.
FAU - Shi, Ying-Rui
AU  - Shi YR
AD  - Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of 
      Medicine, Changsha, China.
FAU - Jin, Feng
AU  - Jin F
AD  - Guizhou Cancer Hospital of Guizhou Medical University, Guiyang, China.
FAU - Xu, Ruilian
AU  - Xu R
AD  - Shenzhen People's Hospital, Shenzhen, China.
FAU - Pan, Jianji
AU  - Pan J
AD  - Fujian Provincial Cancer Hospital, Fuzhou, China.
FAU - Qu, Shenhong
AU  - Qu S
AD  - The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
FAU - Li, Ping
AU  - Li P
AD  - West China Hospital of Sichuan University, Chengdu, China.
FAU - Hu, Chunhong
AU  - Hu C
AD  - The Second Xiangya Hospital of Central South University, Changsha, China.
FAU - Liu, Yi-Chun
AU  - Liu YC
AD  - Taichung Veterans General Hospital, Taichung, Taiwan.
FAU - Jiang, Yi
AU  - Jiang Y
AD  - Cancer Hospital of Shantou University Medical College, Shantou, China.
FAU - He, Xia
AU  - He X
AD  - Jiangsu Cancer Hospital, Nanjing, China.
FAU - Wang, Hung-Ming
AU  - Wang HM
AD  - Chang Gung Memorial Hospital, Taoyuan, Taiwan.
FAU - Lim, Wan-Teck
AU  - Lim WT
AUID- ORCID: 0000-0002-4655-0206
AD  - National Cancer Centre, Singapore City, Singapore.
FAU - Liao, Wangjun
AU  - Liao W
AD  - Nanfang Hospital, Guangzhou, China.
FAU - He, Xiaohui
AU  - He X
AD  - Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical 
      College, Beijing, China.
FAU - Chen, Xiaozhong
AU  - Chen X
AD  - Zhejiang Cancer Hospital, Hangzhou, China.
FAU - Liu, Zhigang
AU  - Liu Z
AUID- ORCID: 0000-0003-4043-3196
AD  - The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
FAU - Yuan, Xianglin
AU  - Yuan X
AD  - Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Li, Qi
AU  - Li Q
AD  - Shanghai General Hospital, Shanghai, China.
FAU - Lin, Xiaoyan
AU  - Lin X
AD  - Fujian Medical University Union Hospital, Fuzhou, China.
FAU - Jing, Shanghua
AU  - Jing S
AD  - The Fourth Hospital of Hebei Medical University Hebei Cancer Hospital, 
      Shijiazhuang, China.
FAU - Chen, Yanju
AU  - Chen Y
AD  - Hainan General Hospital, Haikou, China.
FAU - Lu, Yin
AU  - Lu Y
AD  - Liuzhou Worker's Hospital, Liuzhou, China.
FAU - Hsieh, Ching-Yun
AU  - Hsieh CY
AD  - China Medical University Hospital, Taichung, Taiwan.
FAU - Yang, Muh-Hwa
AU  - Yang MH
AUID- ORCID: 0000-0002-8918-1244
AD  - Taipei Veterans General Hospital, Taipei, Taiwan.
FAU - Yen, Chia-Jui
AU  - Yen CJ
AD  - National Cheng Kung University, Tainan, Taiwan.
FAU - Samol, Jens
AU  - Samol J
AD  - Tan Tock Seng Hospital, Singapore City, Singapore.
AD  - Johns Hopkins University, Baltimore, MD, USA.
FAU - Feng, Hui
AU  - Feng H
AD  - Shanghai Junshi Biosciences, Shanghai, China.
AD  - TopAlliance Biosciences, Rockville, MD, USA.
FAU - Yao, Sheng
AU  - Yao S
AD  - Shanghai Junshi Biosciences, Shanghai, China.
AD  - TopAlliance Biosciences, Rockville, MD, USA.
FAU - Keegan, Patricia
AU  - Keegan P
AUID- ORCID: 0000-0002-7266-395X
AD  - TopAlliance Biosciences, Rockville, MD, USA.
FAU - Xu, Rui-Hua
AU  - Xu RH
AUID- ORCID: 0000-0001-9771-8534
AD  - 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, China. xurh@sysucc.org.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT03581786
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210802
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 8JXN261VVA (toripalimab)
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Gemcitabine)
SB  - IM
CIN - Nat Med. 2021 Sep;27(9):1512-1513. PMID: 34518676
EIN - Nat Med. 2022 Jan;28(1):214. PMID: 35027760
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects
MH  - Antineoplastic Agents, Immunological/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - B7-H1 Antigen/antagonists & inhibitors/genetics
MH  - Cisplatin/administration & dosage/adverse effects
MH  - Deoxycytidine/administration & dosage/adverse effects/analogs & derivatives
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nasopharyngeal Carcinoma/*drug therapy/immunology/pathology
MH  - Neoplasm Recurrence, Local/*drug therapy/immunology/pathology
MH  - Progression-Free Survival
MH  - Gemcitabine
EDAT- 2021/08/04 06:00
MHDA- 2021/10/09 06:00
CRDT- 2021/08/03 06:36
PHST- 2021/05/04 00:00 [received]
PHST- 2021/06/21 00:00 [accepted]
PHST- 2021/08/04 06:00 [pubmed]
PHST- 2021/10/09 06:00 [medline]
PHST- 2021/08/03 06:36 [entrez]
AID - 10.1038/s41591-021-01444-0 [pii]
AID - 10.1038/s41591-021-01444-0 [doi]
PST - ppublish
SO  - Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 
      2.