PMID- 37247023
OWN - NLM
STAT- MEDLINE
DCOM- 20230811
LR  - 20230812
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 72
IP  - 9
DP  - 2023 Sep
TI  - Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with 
      lenvatinib and Gemox chemotherapy as first-line treatment in advanced 
      intrahepatic cholangiocarcinoma: a multicenter real-world study.
PG  - 2949-2960
LID - 10.1007/s00262-023-03466-8 [doi]
AB  - BACKGROUND: A programmed cell death protein-1 (PD-1) inhibitor combined with 
      lenvatinib and Gemox chemotherapy as first-line therapy demonstrated high 
      anti-tumor activity against biliary tract cancer in phase II clinical trials. 
      Herein, we aimed to investigate the efficacy and safety for advanced intrahepatic 
      cholangiocarcinoma (ICC) in a multicenter real-world study. METHODS: Patients 
      with advanced ICC who received PD-1 inhibitor combined with lenvatinib and Gemox 
      chemotherapy were retrospectively screened at two medical centers. The primary 
      endpoints were overall survival (OS) and progression-free survival (PFS), whereas 
      the secondary endpoints were objective response rate (ORR), disease control rate 
      (DCR), and safety. Prognostic factors for survival were analyzed. RESULTS: 
      Fifty-three patients with advanced ICC were included in this study. The median 
      follow-up time was 13.7 (95% confidence interval (CI): 12.9-17.2) months. The 
      median OS and PFS were 14.3 (95% CI: 11.3-NR) and 8.63 (95% CI: 7.17-11.6) 
      months, respectively. The ORR, DCR, and clinical benefit rate were 52.8, 94.3, 
      and 75.5%, respectively. In the multivariate analysis, the tumor burden score 
      (TBS), tumor-node metastasis classification (TNM) stage, and PD-L1 expression 
      were independent prognostic factors for OS and PFS. All patients experienced 
      adverse events (AEs), 41.5% (22/53) experienced grade 3 or 4 AEs, including 
      fatigue (8/53, 15.1%) and myelosuppression (7/53, 13.2%). No grade 5 AEs were 
      reported. CONCLUSION: PD-1 inhibitors combined with lenvatinib and Gemox 
      chemotherapy represent an effective and tolerable regimen for advanced ICC in a 
      multicenter retrospective real-world study. TBS, TNM stage, and PD-L1 expression 
      can be used as potential prognostic factors for OS and PFS.
CI  - (c) 2023. The Author(s).
FAU - Zhu, Chengpei
AU  - Zhu C
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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China.
FAU - Li, Hu
AU  - Li H
AD  - Department of Hepatobiliary Surgery, The Fifth Medical Center of PLA General 
      Hospital, No. 100 Middle Road of West 4th Ring Road, Fengtai District, Beijing, 
      100039, 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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China.
FAU - Wang, Shanshan
AU  - Wang S
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), #1 Shuaifuyuan, 
      Wangfujing, 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), #1 Shuaifuyuan, 
      Wangfujing, 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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, 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), #1 Shuaifuyuan, 
      Wangfujing, 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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China.
FAU - Zhang, Longhao
AU  - Zhang L
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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China.
FAU - Ning, Cong
AU  - Ning C
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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China.
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), #1 Shuaifuyuan, 
      Wangfujing, 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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China.
FAU - Chao, Jiashuo
AU  - Chao 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), #1 Shuaifuyuan, 
      Wangfujing, 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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China.
FAU - Sang, Xinting
AU  - Sang X
AUID- ORCID: 0000-0003-1952-0527
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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China. sangxt@pumch.cn.
FAU - Zhu, Zhenyu
AU  - Zhu Z
AUID- ORCID: 0000-0001-5344-3161
AD  - Department of Hepatobiliary Surgery, The Fifth Medical Center of PLA General 
      Hospital, No. 100 Middle Road of West 4th Ring Road, Fengtai District, Beijing, 
      100039, China. zhuzy302@163.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), #1 Shuaifuyuan, 
      Wangfujing, Beijing, 100730, China. zhaoht@pumch.cn.
LA  - eng
GR  - Y-HR2020QN-0414/CSCO-hengrui Cancer Research Fund/
GR  - Y-HR2020MS-0415/CSCO-hengrui Cancer Research Fund/
GR  - Y-HR2019-0239/CSCO-hengrui Cancer Research Fund/
GR  - 2021-I2M-1-003/CAMS Innovation Fund for Medical Sciences/
GR  - 2022-I2M-C&T-A-003/CAMS Innovation Fund for Medical Sciences/
GR  - 2022-PUMCH-B-128/National High Level Hospital Clinical Research Funding/
GR  - Y-MSDZD2021-0213/CSCO-MSD Cancer Research Fund/
PT  - Journal Article
PT  - Multicenter Study
DEP - 20230529
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - EE083865G2 (lenvatinib)
RN  - 0 (B7-H1 Antigen)
SB  - IM
MH  - Humans
MH  - Immune Checkpoint Inhibitors
MH  - B7-H1 Antigen
MH  - Retrospective Studies
MH  - Prognosis
MH  - *Cholangiocarcinoma/drug therapy
MH  - *Bile Duct Neoplasms/drug therapy
MH  - Bile Ducts, Intrahepatic
PMC - PMC10412480
OTO - NOTNLM
OT  - Advanced intrahepatic cholangiocarcinoma
OT  - Gemox chemotherapy
OT  - Lenvatinib
OT  - PD-1 inhibitor
OT  - Systemic therapy
COIS- The authors have no relevant financial or non-financial interests to disclose.
EDAT- 2023/05/29 13:05
MHDA- 2023/08/11 06:43
PMCR- 2023/05/29
CRDT- 2023/05/29 11:06
PHST- 2023/02/13 00:00 [received]
PHST- 2023/05/10 00:00 [accepted]
PHST- 2023/08/11 06:43 [medline]
PHST- 2023/05/29 13:05 [pubmed]
PHST- 2023/05/29 11:06 [entrez]
PHST- 2023/05/29 00:00 [pmc-release]
AID - 10.1007/s00262-023-03466-8 [pii]
AID - 3466 [pii]
AID - 10.1007/s00262-023-03466-8 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2023 Sep;72(9):2949-2960. doi: 
      10.1007/s00262-023-03466-8. Epub 2023 May 29.