PMID- 36753026
OWN - NLM
STAT- MEDLINE
DCOM- 20230529
LR  - 20230530
IS  - 1936-0541 (Electronic)
IS  - 1936-0533 (Print)
IS  - 1936-0533 (Linking)
VI  - 17
IP  - 3
DP  - 2023 Jun
TI  - Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 
      378 unresectable hepatocellular carcinoma patients.
PG  - 709-719
LID - 10.1007/s12072-022-10480-y [doi]
AB  - INTRODUCTION: Combining lenvatinib with a programmed cell death protein-1 (PD-1) 
      inhibitor has been explored for the treatment of un-resectable hepatocellular 
      carcinoma (uHCC). This study aimed to investigate the real-world efficacy of and 
      prognostic factors for survival associated with lenvatinib plus PD-1 inhibitor 
      treatment in a large cohort of Asian uHCC patients even the global LEAP-002 study 
      failed to achieve the primary endpoints. METHODS: Patients with uHCC treated with 
      lenvatinib and PD-1 inhibitors were included. The primary endpoints were overall 
      survival (OS) and progression-free survival (PFS), and the secondary endpoints 
      were the objective response rate (ORR) and adverse events (AEs). Prognostic 
      factors for survival were also analyzed. RESULTS: A total of 378 uHCC patients 
      from two medical centers in China were assessed retrospectively. The median 
      patient age was 55 years, and 86.5% of patients were male. Hepatitis B virus 
      (HBV) infection (89.9%) was the dominant etiology of uHCC. The median OS was 17.8 
      (95% confidence interval (CI) 14.0-21.6) months. The median PFS was 6.9 (95% CI 
      6.0-7.9) months. The best ORR and disease control rate (DCR) were 19.6% and 
      73.5%, respectively. In multivariate analysis, Child‒Pugh grade, Barcelona Clinic 
      Liver Cancer stage, Eastern Cooperative Oncology Group performance status score, 
      involved organs, tumor burden score, and combination with local therapy were 
      independent prognostic factors for OS. A total of 100% and 57.9% of patients 
      experienced all-grade and grade 3/4 treatment-emergent AEs, respectively. 
      CONCLUSION: This real-world study of lenvatinib plus PD-1 inhibitor treatment 
      demonstrated long survival and considerable ORRs and DCRs in uHCC patients in 
      China. The tolerability of combination therapy was acceptable but must be 
      monitored closely.
CI  - (c) 2023. The Author(s).
FAU - Yang, Xu
AU  - Yang X
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Chen, Bowen
AU  - Chen B
AD  - Peking University 302 Clinical Medical School, Beijing, China.
AD  - Comprehensive Liver Cancer Center, The Fifth Medical Center of the PLA General 
      Hospital, Beijing, 100039, China.
FAU - Wang, Yanyu
AU  - Wang Y
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Wang, Yunchao
AU  - Wang Y
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Long, Junyu
AU  - Long J
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Zhang, Nan
AU  - Zhang N
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Xue, Jingnan
AU  - Xue J
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Xun, Ziyu
AU  - Xun Z
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Zhang, Linzhi
AU  - Zhang L
AD  - Comprehensive Liver Cancer Center, The Fifth Medical Center of the PLA General 
      Hospital, Beijing, 100039, China.
AD  - Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
FAU - Cheng, Jiamin
AU  - Cheng J
AD  - Comprehensive Liver Cancer Center, The Fifth Medical Center of the PLA General 
      Hospital, Beijing, 100039, China.
FAU - Lei, Jin
AU  - Lei J
AD  - Comprehensive Liver Cancer Center, The Fifth Medical Center of the PLA General 
      Hospital, Beijing, 100039, China.
AD  - Guizhou Medical University, Guiyang, China.
FAU - Sun, Huishan
AU  - Sun H
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Li, Yiran
AU  - Li Y
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Lin, Jianzhen
AU  - Lin J
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Xie, Fucun
AU  - Xie F
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Wang, Dongxu
AU  - Wang D
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Pan, Jie
AU  - Pan J
AD  - Department of Radiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Hu, Ke
AU  - Hu K
AD  - Center of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of 
      Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Guan, Mei
AU  - Guan M
AD  - Departmentof Medical Oncology, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Huo, Li
AU  - Huo L
AD  - Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Shi, Jie
AU  - Shi J
AD  - Department of Pathology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Yu, Lingxiang
AU  - Yu L
AD  - Senior Department of Oncology, The Fifth Medical Center of the PLA General 
      Hospital, Beijing, China.
FAU - Zhou, Lin
AU  - Zhou L
AD  - Senior Department of Oncology, The Fifth Medical Center of the PLA General 
      Hospital, Beijing, China.
FAU - Zhou, Jinxue
AU  - Zhou J
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer 
      Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
FAU - Lu, Zhenhui
AU  - Lu Z
AD  - Hepatobiliary and Pancreatic Surgery, Shenzhen Qianhai Shekou Free Trade Zone 
      Hospital, Shenzhen, China.
FAU - Yang, Xiaobo
AU  - Yang X
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Mao, Yilei
AU  - Mao Y
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Sang, Xinting
AU  - Sang X
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China.
FAU - Lu, Yinying
AU  - Lu Y
AD  - Peking University 302 Clinical Medical School, Beijing, China. 
      luyinying2017@sina.com.
AD  - Comprehensive Liver Cancer Center, The Fifth Medical Center of the PLA General 
      Hospital, Beijing, 100039, China. luyinying2017@sina.com.
FAU - Zhao, Haitao
AU  - Zhao H
AUID- ORCID: 0000-0002-3444-8044
AD  - Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare 
      Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical 
      Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, 100730, China. 
      zhaoht@pumch.cn.
LA  - eng
GR  - 2021-I2M-1-061/Chinese Academy of Medical Sciences Initiative for Innovative 
      Medicine/
GR  - 2021-1-I2M-003/Chinese Academy of Medical Sciences Initiative for Innovative 
      Medicine/
GR  - 2019XK320006/CAMS Clinical and Translational Medicine Research Funds/
GR  - Y-HR2019-0239/CSCO-Hengrui Cancer Research Fund/
GR  - Y-HR2020MS-0414/CSCO-Hengrui Cancer Research Fund/
GR  - Y-HR2020QN-0415/CSCO-Hengrui Cancer Research Fund/
GR  - Y-MSDZD2021-0213/CSCO-MSD Cancer Research Fund/
PT  - Journal Article
DEP - 20230208
PL  - United States
TA  - Hepatol Int
JT  - Hepatology international
JID - 101304009
RN  - EE083865G2 (lenvatinib)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Female
MH  - *Carcinoma, Hepatocellular/drug therapy
MH  - Immune Checkpoint Inhibitors
MH  - *Liver Neoplasms/drug therapy
MH  - Prognosis
MH  - Retrospective Studies
MH  - *Hepatitis B
MH  - Hepatitis B virus
PMC - PMC9907200
OTO - NOTNLM
OT  - Adverse events
OT  - Hepatitis B virus
OT  - Hepatocellular carcinoma
OT  - Lenvatinib
OT  - Nivolumab
OT  - PD-1 inhibitor
OT  - Pembrolizumab
OT  - Un-resectable
COIS- Xu Yang, Bowen Chen, Yanyu Wang, Yunchao Wang, Junyu Long, Nan Zhang, Jingnan 
      Xue, Ziyu Xun, Linzhi Zhang, Jiamin Cheng, Jin Lei, Huishan Sun, Yiran Li, 
      Jianzhen Lin, Fucun Xie, Dongxu Wang, Jie Pan, Ke Hu, Mei Guan, Li Huo, Jie Shi, 
      Lingxiang Yu, Lin Zhou, Jinxue Zhou, Zhenhui Lu, Xiaobo Yang, Yilei Mao, Xinting 
      Sang, Yinying Lu, Haitao Zhao declare no conflict of interest.
EDAT- 2023/02/09 06:00
MHDA- 2023/05/29 06:42
PMCR- 2023/02/08
CRDT- 2023/02/08 11:22
PHST- 2022/10/11 00:00 [received]
PHST- 2022/12/27 00:00 [accepted]
PHST- 2023/05/29 06:42 [medline]
PHST- 2023/02/09 06:00 [pubmed]
PHST- 2023/02/08 11:22 [entrez]
PHST- 2023/02/08 00:00 [pmc-release]
AID - 10.1007/s12072-022-10480-y [pii]
AID - 10480 [pii]
AID - 10.1007/s12072-022-10480-y [doi]
PST - ppublish
SO  - Hepatol Int. 2023 Jun;17(3):709-719. doi: 10.1007/s12072-022-10480-y. Epub 2023 
      Feb 8.