PMID- 34033975
OWN - NLM
STAT- MEDLINE
DCOM- 20210914
LR  - 20210914
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 16
IP  - 9
DP  - 2021 Sep
TI  - Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or 
      Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial.
PG  - 1512-1522
LID - S1556-0864(21)02176-6 [pii]
LID - 10.1016/j.jtho.2021.05.005 [doi]
AB  - INTRODUCTION: Tislelizumab, an anti-programmed cell death protein-1 antibody, was 
      specifically engineered to minimize FcɣR macrophage binding to abrogate 
      antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab 
      plus chemotherapy may improve clinical outcomes in patients with advanced 
      nonsquamous NSCLC (nsq-NSCLC). METHODS: In this open-label phase 3 trial 
      (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB 
      or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus 
      platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: 
      platinum and pemetrexed alone Q3W during induction treatment, followed by 
      intravenous maintenance pemetrexed Q3W. The primary end point was 
      progression-free survival (PFS) assessed by an independent review committee; 
      clinical response and safety and tolerability were secondary end points. RESULTS: 
      Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a 
      median study follow-up of 9.8 months, PFS was significantly longer with 
      tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 
      versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 
      0.0044). In addition, response rates were higher and response duration was longer 
      with combination therapy versus chemotherapy alone. Hematologic adverse events 
      (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 
      2 in severity. The most common grade greater than or equal to 3 AEs were 
      associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and 
      leukopenia (21.6% [A]; 14.5% [B]). CONCLUSIONS: Addition of tislelizumab to 
      chemotherapy resulted in significantly prolonged PFS, higher response rates, and 
      longer response duration compared with chemotherapy alone, identifying a new 
      potential option for first-line treatment of advanced nsq-NSCLC irrespective of 
      disease stage.
CI  - Copyright (c) 2021 International Association for the Study of Lung Cancer. 
      Published by Elsevier Inc. All rights reserved.
FAU - Lu, Shun
AU  - Lu S
AD  - Shanghai Chest Hospital, Department of Oncology, Shanghai, People's Republic of 
      China. Electronic address: shunlu@sjtu.edu.cn.
FAU - Wang, Jie
AU  - Wang J
AD  - Cancer Hospital Chinese Academy of Medical Sciences, Beijing, Department of 
      Medical Oncology, People's Republic of China.
FAU - Yu, Yan
AU  - Yu Y
AD  - Harbin Medical University Cancer Hospital, Department of Thoracic Oncology, 
      Harbin, People's Republic of China.
FAU - Yu, Xinmin
AU  - Yu X
AD  - Zhejiang Cancer Hospital, Department of Thoracic Oncology, Hangzhou, People's 
      Republic of China.
FAU - Hu, Yanping
AU  - Hu Y
AD  - Hubei Cancer Hospital, Department of Thoracic Oncology, Wuhan, People's Republic 
      of China.
FAU - Ai, Xinghao
AU  - Ai X
AD  - Shanghai Chest Hospital, Department of Oncology, Shanghai, People's Republic of 
      China.
FAU - Ma, Zhiyong
AU  - Ma Z
AD  - The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, 
      Department of Medical Oncology, Zhengzhou, People's Republic of China.
FAU - Li, Xingya
AU  - Li X
AD  - The First Affiliated Hospital of Zhengzhou University, Department of Oncology, 
      Zhengzhou, People's Republic of China.
FAU - Zhuang, Wu
AU  - Zhuang W
AD  - Fujian Cancer Hospital, Department of Medical Oncology, Fuzhou, People's Republic 
      of China.
FAU - Liu, Yunpeng
AU  - Liu Y
AD  - The First Hospital of China Medical University, Department of Medical Oncology, 
      Shenyang, People's Republic of China.
FAU - Li, Weidong
AU  - Li W
AD  - Cancer Center of Guangzhou Medical University, Cancer Center Department, 
      Guangzhou, People's Republic of China.
FAU - Cui, Jiuwei
AU  - Cui J
AD  - The First Hospital of Jilin University, Cancer Center Department, Changchun, 
      People's Republic of China.
FAU - Wang, Dong
AU  - Wang D
AD  - Daping Hospital, Third Military Medical University, Cancer Center Department, 
      Chongqing, People's Republic of China.
FAU - Liao, Wangjun
AU  - Liao W
AD  - Nanfang Hospital of Southern Medical University, Department of Oncology, 
      Guangzhou, People's Republic of China.
FAU - Zhou, Jianying
AU  - Zhou J
AD  - The First Affiliated Hospital of Zhejiang University, Department of Respiratory 
      Disease, Hangzhou, People's Republic of China.
FAU - Wang, Zhehai
AU  - Wang Z
AD  - Shandong Cancer Hospital, Department of Internal Medicine-Oncology, Jinan, 
      People's Republic of China.
FAU - Sun, Yuping
AU  - Sun Y
AD  - Jinan Central Hospital, Department of Oncology, Jinan, People's Republic of 
      China.
FAU - Qiu, Xiusong
AU  - Qiu X
AD  - BeiGene (Beijing) Co., Ltd., Department of Clinical Development, Beijing, 
      People's Republic of China.
FAU - Gao, Jie
AU  - Gao J
AD  - BeiGene (Beijing) Co., Ltd., Beijing, People's Republic of China.
FAU - Bao, Yuanyuan
AU  - Bao Y
AD  - BeiGene (Beijing) Co., Ltd., Department of Medical Oncology, Beijing, People's 
      Republic of China.
FAU - Liang, Liang
AU  - Liang L
AD  - BeiGene (Beijing) Co., Ltd., Department of Clinical Biomarkers, Beijing, People's 
      Republic of China.
FAU - Wang, Mengzhao
AU  - Wang M
AD  - Peking Union Medical College Hospital, Department of Pulmonary Medicine, Beijing, 
      People's Republic of China.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210523
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0KVO411B3N (tislelizumab)
SB  - IM
CIN - J Thorac Oncol. 2021 Sep;16(9):1434-1436. PMID: 34425995
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - Humans
MH  - *Lung Neoplasms/drug therapy
OTO - NOTNLM
OT  - Non-squamous non-small cell lung cancer
OT  - Platinum-pemetrexed
OT  - Stage IIIB
OT  - Stage IV
OT  - Tislelizumab
EDAT- 2021/05/26 06:00
MHDA- 2021/09/15 06:00
CRDT- 2021/05/25 20:14
PHST- 2021/03/27 00:00 [received]
PHST- 2021/05/04 00:00 [revised]
PHST- 2021/05/10 00:00 [accepted]
PHST- 2021/05/26 06:00 [pubmed]
PHST- 2021/09/15 06:00 [medline]
PHST- 2021/05/25 20:14 [entrez]
AID - S1556-0864(21)02176-6 [pii]
AID - 10.1016/j.jtho.2021.05.005 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2021 Sep;16(9):1512-1522. doi: 10.1016/j.jtho.2021.05.005. Epub 
      2021 May 23.