PMID- 32780516
OWN - NLM
STAT- MEDLINE
DCOM- 20210720
LR  - 20210720
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 9
IP  - 19
DP  - 2020 Oct
TI  - Pattern and impact of hepatic adverse events encountered during immune checkpoint 
      inhibitors - A territory-wide cohort study.
PG  - 7052-7061
LID - 10.1002/cam4.3378 [doi]
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used in the 
      treatment of cancers. We aimed to evaluate the incidence and prognostic impact of 
      hepatic adverse events (AEs) in a territory-wide cohort of patients who received 
      ICIs. METHODS: Patients were identified from a territory-wide database who 
      received ICIs in 2014-2018. Hepatic AEs were defined as any elevation of liver 
      biochemistries including serum alanine aminotransferase (ALT), aspartate 
      aminotransferase (AST), or total bilirubin levels. Hepatic AEs were graded 
      according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 
      RESULTS: Total of 1480 patients were identified (mean age 60 years, male 65.5%) 
      and the commonest malignancies being lung cancer (39.6%), liver cancer (16.5%), 
      and gastrointestinal cancer (10.0%). Grade 1-2 and grade 3-4 hepatic AEs occurred 
      in 41.3% and 14.9% of patients during ICI treatment, respectively. Patients with 
      liver cancer had the highest rate of hepatic AEs (grade 1-2:54.1%; grade 
      3-4:32.8%). Among 711 patients with hepatic AEs, 383 (53.9%) had raised ALT/AST 
      only, and 328 (46.1%) had concomitant raised ALT/AST and bilirubin levels. In the 
      whole cohort, median overall survival of patients without any hepatic AEs, grade 
      1-2 and grade 3-4 hepatic AEs during ICI treatment was 9.0 months, 7.2 months, 
      and 3.3 months (P < .001), respectively. Similar results on overall survival were 
      obtained among different types of cancers. CONCLUSIONS: Hepatic AEs occur in more 
      than half of patients receiving ICIs for cancer treatment, with approximately 15% 
      being grade 3-4 AEs. Occurrence of hepatic AEs is associated with worse 
      prognosis.
CI  - (c) 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Chan, Stephen Lam
AU  - Chan SL
AD  - Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
FAU - Yip, Terry Cheuk-Fung
AU  - Yip TC
AD  - Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
AD  - Medical Data Analytics Centre, Pathology, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
FAU - Wong, Vincent Wai-Sun
AU  - Wong VW
AD  - Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
AD  - Medical Data Analytics Centre, Pathology, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
FAU - Tse, Yee-Kit
AU  - Tse YK
AD  - Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
AD  - Medical Data Analytics Centre, Pathology, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
FAU - Yuen, Becky Wing-Yan
AU  - Yuen BW
AD  - Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
FAU - Luk, Hester Wing-Sum
AU  - Luk HW
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
FAU - Lui, Rashid Nok-Shun
AU  - Lui RN
AD  - Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
AD  - Medical Data Analytics Centre, Pathology, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
FAU - Chan, Henry Lik-Yuen
AU  - Chan HL
AD  - Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
AD  - Medical Data Analytics Centre, Pathology, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
FAU - Mok, Tony Shu-Kam
AU  - Mok TS
AD  - Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
FAU - Wong, Grace Lai-Hung
AU  - Wong GL
AUID- ORCID: 0000-0002-2863-9389
AD  - Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
AD  - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
AD  - Medical Data Analytics Centre, Pathology, The Chinese University of Hong Kong, 
      Hong Kong SAR, China.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200811
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Biomarkers)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Aged
MH  - Alanine Transaminase/blood
MH  - Aspartate Aminotransferases/blood
MH  - Bilirubin/blood
MH  - Biomarkers/blood
MH  - Chemical and Drug Induced Liver Injury/blood/diagnosis/*epidemiology/mortality
MH  - Databases, Factual
MH  - Female
MH  - Hong Kong/epidemiology
MH  - Humans
MH  - Immune Checkpoint Inhibitors/*adverse effects
MH  - Incidence
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/diagnosis/*drug therapy/immunology
MH  - Retrospective Studies
MH  - Risk Assessment
MH  - Risk Factors
MH  - Treatment Outcome
PMC - PMC7541136
OTO - NOTNLM
OT  - hepatic adverse events
OT  - immunotherapy
OT  - liver cancer
OT  - programmed cell death-1
COIS- Stephen Chan has served as an advisory committee member for MSD, Astra-Zeneca, 
      Eisai and Ipsen. Terry Yip has served as a speaker for Gilead Sciences. Vincent 
      Wong has served as an advisory committee member for 3V-BIO, AbbVie, Allergan, 
      Echosens, Gilead Sciences, Janssen, Novartis, Novo Nordisk, Perspectum 
      Diagnostics, Pfizer and Terns; and a speaker for Bristol-Myers Squibb, Echosens, 
      Gilead Sciences and Merck. He has also received a research grant from Gilead 
      Sciences. Henry Chan has served as an advisory committee member for AbbVie, 
      Aligos, Aptorum, Altimmune, Arbutus, ContraVir, Intellia, Janssen, Gilead, 
      Medimmune, Roche, Vaccitech, VenetoRx, Vir Biotechnology and GRAIL; and as a 
      speaker for AbbVie, Gilead and Roche. Tony Mok has served as a member of the 
      board of directors for AstraZeneca, Chi-Med, and Sanomics, has received grants or 
      research support from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck 
      Sharp & Dohme, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, and XCovery, 
      speakers' fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli 
      Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Taiho, and Takeda 
      Oncology, honoraria from ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, 
      Bristol-Myers Squibb, Celgene, Eli Lilly, Fishawack Facilitate, Ignyta, Janssen, 
      Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex Pharmaceuticals, Pfizer, 
      Roche/Genentech, SFJ Pharmaceuticals, Takeda Oncology, and Vertex 
      Pharmaceuticals, is a major stockholder in Sanomics, and is an advisory board 
      member for ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, Bristol-Myers 
      Squibb, Celgene, ChiMed, Cirina, Clovis Oncology, Eli Lilly, Fishawack 
      Facilitate, geneDecode Co, Ignyta, Janssen, Pfizer, Merck Serono, Merck Sharp & 
      Dohme, Novartis, Roche/Genentech, SFJ Pharmaceuticals, Takeda, and Vertex 
      Pharmaceuticals. Grace Wong has served as an advisory committee member for Gilead 
      Sciences and Janssen, and as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, 
      Echosens, Gilead Sciences, Janssen, and Roche. The other authors declare no 
      competing interests.
EDAT- 2020/08/12 06:00
MHDA- 2021/07/21 06:00
PMCR- 2020/08/11
CRDT- 2020/08/12 06:00
PHST- 2020/05/09 00:00 [received]
PHST- 2020/07/08 00:00 [revised]
PHST- 2020/07/27 00:00 [accepted]
PHST- 2020/08/12 06:00 [pubmed]
PHST- 2021/07/21 06:00 [medline]
PHST- 2020/08/12 06:00 [entrez]
PHST- 2020/08/11 00:00 [pmc-release]
AID - CAM43378 [pii]
AID - 10.1002/cam4.3378 [doi]
PST - ppublish
SO  - Cancer Med. 2020 Oct;9(19):7052-7061. doi: 10.1002/cam4.3378. Epub 2020 Aug 11.