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Nivolumab versus Docetaxel in a Predominantly Chinese Patient Population with Previously Treated Advanced Non-Small-Cell Lung Cancer: CheckMate 078 Randomised Phase 3 Clinical Trial

31 Pages Posted: 25 Sep 2018

See all articles by Yi-Long Wu

Yi-Long Wu

Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangdong Lung Cancer Institute, Department of Pulmonary Oncology

Shun Lu

Shanghai Jiao Tong University (SJTU)

Ying Cheng

Jilin Cancer Hospital

Caicun Zhou

Tongji University

Jie Wang

Chinese Academy of Sciences (CAS)

Tony Mok

The Chinese University of Hong Kong (CUHK)

Li Zhang

Sun Yat-Sen University (SYSU)

Haiyan Tu

Guangdong Academy of Medical Sciences

Lin Wu

Hunan Cancer Hospital

Jifeng Feng

Jiangsu Cancer Hospital - Department of Medical Oncology; Nanjing Medical University - Jiangsu Institute of Cancer Research; Nanjing Medical University - Affiliated Cancer Hospital

Yiping Zhang

Zhejiang Cancer Hospital

Alexander Valerievich Luft

Leningrad Regional Clinical Hospital

Jianying Zhou

Zhejiang University

Zhiyong Ma

Henan Cancer Hospital

You Lu

Sichuan University - West China Hospital

Chenping Hu

Central South University

Yuankai Shi

Chinese Academy of Medical Sciences - Peking Union Medical College; Chinese Academy of Sciences (CAS) - Beijing Key Laboratory of Molecular Imaging; National Cancer Center Hospital; Chinese Academy of Medical Sciences

Christine Baudelet

Bristol-Myers Squibb

Junliang Cai

Bristol-Myers Squibb

Jianhua Chang

Fudan University

More...

Abstract

BACKGROUND: Data on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly Chinese patient population with previously treated non-small-cell lung cancer (NSCLC).

METHODS: CheckMate 078 was a randomised, open-label, phase 3 clinical trial enrolling patients from China, Russia, and Singapore with NSCLC whose disease progressed during/after platinum-based doublet chemotherapy. Patients (N=504) were included regardless of tumour histology and programmed death ligand 1 (PD-L1) expression; those with EGFR/ALK alterations were excluded. Patients were randomised 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks), stratified by performance status, histology, and tumour PD-L1 expression. The primary endpoint was overall survival (OS); secondary endpoints included objective response rate (ORR) and progression-free survival.

FINDINGS: OS was significantly improved with nivolumab (n=338) versus docetaxel (n=166); median OS (95% CI), 12·0 (10·4-14·0) versus 9·6 (7·6- 11·2) months, respectively; hazard ratio (97·7% CI), 0·68 (0·52-0·90); p=0·0006. ORR was 17% with nivolumab versus 4% with docetaxel; median duration of response was not reached versus 5·3 months. Minimum follow-up was 8·8 months. The frequency of grade ≥3 treatment-related adverse events was 10% with nivolumab and 48% with docetaxel.

INTERPRETATION: This is the first phase 3 study in a predominantly Chinese population reporting results with a PD-1 inhibitor. In this population with previously treated advanced NSCLC, nivolumab improved OS versus docetaxel. Results were consistent with global CheckMate 017 and 057 studies.

CLINICAL TRIAL NUMBER: CheckMate 078 is registered on ClinicalTrials.gov, number NCT02613507.

FUNDING STATEMENT: The study was funded by Bristol-Myers Squibb. Bristol-Myers Squibb was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

DECLARATION OF INTERESTS: Y-LW has received grants from Roche; has received personal fees from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi; and has received non-financial support from AstraZeneca. JW has received non-financial support from AstraZeneca. TM has received grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Eisai, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, SFJ Pharmaceuticals, Taiho, Takeda, and XCovery and has received personal fees from ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, BristolMyers Squibb, Celgene, ChiMed, Clovis Oncology, Eli Lilly, Fishawack Facilitate Ltd, Ignyta Inc, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex, Pfizer, Roche/Genentech, SFJ Pharmaceuticals, Taiho, Takeda, and Vertex. CB and J Cai are employees of Bristol-Myers Squibb. All other authors report no competing interests.

ETHICS APPROVAL STATEMENT: The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation guidelines on good clinical practice. The study protocol was approved by an institutional review board or independent ethics committee at each site. An independent data monitoring committee monitored the activity and safety of nivolumab versus docetaxel throughout the study

Keywords: nivolumab; PD-1 inhibitor; non-small-cell lung cancer; NSCLC; China; docetaxel; immunotherapy

Suggested Citation

Wu, Yi-Long and Lu, Shun and Cheng, Ying and Zhou, Caicun and Wang, Jie and Mok, Tony and Zhang, Li and Tu, Haiyan and Wu, Lin and Feng, Jifeng and Zhang, Yiping and Luft, Alexander Valerievich and Zhou, Jianying and Ma, Zhiyong and Lu, You and Hu, Chenping and Shi, Yuankai and Baudelet, Christine and Cai, Junliang and Chang, Jianhua, Nivolumab versus Docetaxel in a Predominantly Chinese Patient Population with Previously Treated Advanced Non-Small-Cell Lung Cancer: CheckMate 078 Randomised Phase 3 Clinical Trial (August 29, 2018). Available at SSRN: https://ssrn.com/abstract=3244996

Yi-Long Wu (Contact Author)

Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangdong Lung Cancer Institute, Department of Pulmonary Oncology ( email )

China

Shun Lu

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Ying Cheng

Jilin Cancer Hospital

Changchun
China

Caicun Zhou

Tongji University

Shanghai
China

Jie Wang

Chinese Academy of Sciences (CAS)

52 Sanlihe Rd.
Datun Road, Anwai
Beijing, Xicheng District 100864
China

Tony Mok

The Chinese University of Hong Kong (CUHK)

Shatin, N.T.
Hong Kong
Hong Kong

Li Zhang

Sun Yat-Sen University (SYSU) ( email )

Guangzhou, Guangdong
China

Haiyan Tu

Guangdong Academy of Medical Sciences

Daxuecheng Outer Ring E Rd,
Panyu Qu
Guangzhou Shi, Guangdong Sheng
China

Lin Wu

Hunan Cancer Hospital

Changsha, 410013
China

Jifeng Feng

Jiangsu Cancer Hospital - Department of Medical Oncology ( email )

Nanjing
China

Nanjing Medical University - Jiangsu Institute of Cancer Research ( email )

Nanjing
China

Nanjing Medical University - Affiliated Cancer Hospital ( email )

Nanjing
China

Yiping Zhang

Zhejiang Cancer Hospital

China

Alexander Valerievich Luft

Leningrad Regional Clinical Hospital

Russia

Jianying Zhou

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Zhiyong Ma

Henan Cancer Hospital

Zhengzhou
China

You Lu

Sichuan University - West China Hospital

No 37, Guoxue Road
Wuhou District
Chengdu, Sichuan Province 610041
China

Chenping Hu

Central South University

Changsha, Hunan 410083
China

Yuankai Shi

Chinese Academy of Medical Sciences - Peking Union Medical College ( email )

Beijing 100021
China
+86-10-87788293 (Phone)
+86-10-87778740 (Fax)

Chinese Academy of Sciences (CAS) - Beijing Key Laboratory of Molecular Imaging

China

National Cancer Center Hospital

Research Center for Cancer Prevention and Screenin
Tokyo
Japan

Chinese Academy of Medical Sciences

NO. 9, Dongdan Santiao
Beijing, Dongcheng District
China

Christine Baudelet

Bristol-Myers Squibb

NY
United States

Junliang Cai

Bristol-Myers Squibb

United States

Jianhua Chang

Fudan University

Beijing West District Baiyun Load 10th
Shanghai, 100045
China

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