PMID- 36928584
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20230412
IS  - 2059-3635 (Electronic)
IS  - 2095-9907 (Print)
IS  - 2059-3635 (Linking)
VI  - 8
IP  - 1
DP  - 2023 Mar 17
TI  - Toripalimab combined with lenvatinib and GEMOX is a promising regimen as 
      first-line treatment for advanced intrahepatic cholangiocarcinoma: a 
      single-center, single-arm, phase 2 study.
PG  - 106
LID - 10.1038/s41392-023-01317-7 [doi]
LID - 106
AB  - Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we 
      report the efficacy and safety of combining toripalimab, lenvatinib, and 
      gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. 
      Thirty patients with pathologically confirmed advanced ICC received intravenous 
      gemcitabine (1 g/m(2)) on Days 1 and 8 and oxaliplatin (85 mg/m(2)) Q3W for six 
      cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) 
      once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and 
      genetic status was investigated in paraffin-embedded tissues using 
      immunohistochemistry and whole-exome sequencing (WES) analysis. The primary 
      endpoint was the objective response rate (ORR). Secondary outcomes included 
      safety, overall survival (OS), progression-free survival (PFS), disease control 
      rate (DCR) and duration of response (DoR). As of July 1, 2022, the median 
      follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients 
      achieved partial response, and one achieved complete response. Patients (21/30) 
      with DNA damage response (DDR)-related gene mutations showed a higher ORR, while 
      patients (14/30) with tumor area positivity >/=1 (PD-L1 staining) showed a trend of 
      high ORR, but without significant difference. The median OS, PFS, and DoR were 
      22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of 
      patients experienced manageable grade >/=3 adverse events (AEs), commonly 
      neutropenia (40.0%) and leukocytopenia (23.3%). In conclusion, toripalimab plus 
      lenvatinib and GEMOX are promising first-line regimens for the treatment of 
      advanced ICC. A phase-III, multicenter, double-blinded, randomized study to 
      validate our findings was approved by the National Medical Products 
      Administration (NMPA, No. 2021LP01825).Trial registration Clinical trials: 
      NCT03951597.
CI  - (c) 2023. The Author(s).
FAU - Shi, Guo-Ming
AU  - Shi GM
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Huang, Xiao-Yong
AU  - Huang XY
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Wu, Dong
AU  - Wu D
AD  - Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Sun, Hui-Chuan
AU  - Sun HC
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Liang, Fei
AU  - Liang F
AD  - Department of Statistics, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Ji, Yuan
AU  - Ji Y
AD  - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Chen, Yi
AU  - Chen Y
AD  - Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
FAU - Yang, Guo-Huan
AU  - Yang GH
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Lu, Jia-Cheng
AU  - Lu JC
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Meng, Xian-Long
AU  - Meng XL
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Wang, Xin-Ying
AU  - Wang XY
AD  - Tianjin Medical Laboratory, BGI-Tianjin, BGI Shenzhen, Tianjin, China.
FAU - Sun, Lei
AU  - Sun L
AUID- ORCID: 0000-0002-8310-1880
AD  - Tianjin Medical Laboratory, BGI-Tianjin, BGI Shenzhen, Tianjin, China.
FAU - Ge, Ning-Ling
AU  - Ge NL
AD  - Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
FAU - Huang, Xiao-Wu
AU  - Huang XW
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Qiu, Shuang-Jian
AU  - Qiu SJ
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Yang, Xin-Rong
AU  - Yang XR
AUID- ORCID: 0000-0002-2716-9338
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Gao, Qiang
AU  - Gao Q
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - He, Yi-Feng
AU  - He YF
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Xu, Yang
AU  - Xu Y
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Sun, Jian
AU  - Sun J
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Ren, Zheng-Gang
AU  - Ren ZG
AD  - Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
FAU - Fan, Jia
AU  - Fan J
AUID- ORCID: 0000-0001-5158-629X
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China. fan.jia@zs-hospital.sh.cn.
FAU - Zhou, Jian
AU  - Zhou J
AUID- ORCID: 0000-0002-2118-1117
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, Fudan University, Shanghai, China. 
      zhou.jian@zs-hospital.sh.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT03951597
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230317
PL  - England
TA  - Signal Transduct Target Ther
JT  - Signal transduction and targeted therapy
JID - 101676423
RN  - 0 (B7-H1 Antigen)
RN  - EE083865G2 (lenvatinib)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 8JXN261VVA (toripalimab)
SB  - IM
MH  - Humans
MH  - B7-H1 Antigen
MH  - *Bile Duct Neoplasms/drug therapy/genetics
MH  - Bile Ducts, Intrahepatic
MH  - *Cholangiocarcinoma/drug therapy/genetics
MH  - Oxaliplatin/therapeutic use
MH  - *Antineoplastic Combined Chemotherapy Protocols/therapeutic use
PMC - PMC10020443
COIS- The authors declare no competing interests.
EDAT- 2023/03/18 06:00
MHDA- 2023/03/22 06:00
PMCR- 2023/03/17
CRDT- 2023/03/17 09:18
PHST- 2022/08/11 00:00 [received]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2022/12/08 00:00 [revised]
PHST- 2023/03/17 09:18 [entrez]
PHST- 2023/03/18 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
PHST- 2023/03/17 00:00 [pmc-release]
AID - 10.1038/s41392-023-01317-7 [pii]
AID - 1317 [pii]
AID - 10.1038/s41392-023-01317-7 [doi]
PST - epublish
SO  - Signal Transduct Target Ther. 2023 Mar 17;8(1):106. doi: 
      10.1038/s41392-023-01317-7.