PMID- 30653255
OWN - NLM
STAT- MEDLINE
DCOM- 20191210
LR  - 20191217
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 145
IP  - 3
DP  - 2019 Aug 1
TI  - A systematic review of adverse events in randomized trials assessing immune 
      checkpoint inhibitors.
PG  - 639-648
LID - 10.1002/ijc.32132 [doi]
AB  - The advent of immune checkpoint-inhibitors (CPI) has transformed treatment for 
      several cancer types. This review was performed to assess the rate of adverse 
      events (AEs) associated with the use of CPI, alone or in combinations. A review 
      of AEs reporting quality was also performed. All publications of Randomized 
      Clinical Trials (RCTs) assessing CPI published before December 2017 were 
      included. To investigate the quality of AEs reporting, a set of items was defined 
      based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, 
      and study-withdrawal related AEs were collected in each treatment category. 
      Specific immune related AEs (irAEs) were also collected when available. Pooled 
      estimates of adverse event rates were calculated by using generalized linear 
      mixed model. A total of 35 RCTs including 16,485 patients were included. The 
      overall quality of AEs reporting was satisfactory, but items pertaining to 
      methods of data collection and analysis were infrequently reported. Grade >/= 3 AEs 
      were reported for 14% (95% CI 12-16) of patients treated with PD(L)-1 inhibitors, 
      34% (95% CI 27-42) of patients treated with CTLA-4 inhibitors, 55% (95% CI 51-59) 
      of patients on CPI combinations and 46% (95% CI 40-53) of patients on 
      immunotherapy-chemotherapy combination. The profile of irAEs was different among 
      the treatment categories. The use of CPI, especially in combination, is 
      associated with significant rates of Grade >/= 3 AEs. Healthcare planning should 
      anticipate the expected high number of patients presenting with irAEs in the 
      future.
CI  - (c) 2019 UICC.
FAU - Arnaud-Coffin, Patrick
AU  - Arnaud-Coffin P
AD  - Department of Medical Oncology, Institut de Cancerologie des Hospices Civils de 
      Lyon (IC-HCL), Pierre-Benite, France.
AD  - Department of ImmuCare (Immunology Cancer Research), Institut de Cancerologie des 
      Hospices Civils de Lyon, Lyon, France.
AD  - Faculte de Medecine Lyon-Sud, Lyon 1 University, EMR 3738, Oullins, France.
FAU - Maillet, Denis
AU  - Maillet D
AD  - Department of Medical Oncology, Institut de Cancerologie des Hospices Civils de 
      Lyon (IC-HCL), Pierre-Benite, France.
AD  - Department of ImmuCare (Immunology Cancer Research), Institut de Cancerologie des 
      Hospices Civils de Lyon, Lyon, France.
FAU - Gan, Hui K
AU  - Gan HK
AD  - Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
AD  - School of Cancer Medicine, La Trobe University, Heidelberg, VIC, Australia.
AD  - Department of Medicine, Melbourne University, Melbourne, VIC, Australia.
FAU - Stelmes, Jean-Jacques
AU  - Stelmes JJ
AD  - Department of Radiation Oncology, University Hospital of Zurich, Zurich, 
      Switzerland.
FAU - You, Benoit
AU  - You B
AD  - Department of Medical Oncology, Institut de Cancerologie des Hospices Civils de 
      Lyon (IC-HCL), Pierre-Benite, France.
AD  - Department of ImmuCare (Immunology Cancer Research), Institut de Cancerologie des 
      Hospices Civils de Lyon, Lyon, France.
AD  - Faculte de Medecine Lyon-Sud, Lyon 1 University, EMR 3738, Oullins, France.
FAU - Dalle, Stephane
AU  - Dalle S
AD  - Department of ImmuCare (Immunology Cancer Research), Institut de Cancerologie des 
      Hospices Civils de Lyon, Lyon, France.
AD  - Faculte de Medecine Lyon-Sud, Lyon 1 University, EMR 3738, Oullins, France.
AD  - Department of Dermatology, Hospices Civils de Lyon, Pierre-Benite, France.
FAU - Peron, Julien
AU  - Peron J
AUID- ORCID: 0000-0002-1709-5152
AD  - Department of Medical Oncology, Institut de Cancerologie des Hospices Civils de 
      Lyon (IC-HCL), Pierre-Benite, France.
AD  - Department of ImmuCare (Immunology Cancer Research), Institut de Cancerologie des 
      Hospices Civils de Lyon, Lyon, France.
AD  - Faculte de Medecine Lyon-Sud, Lyon 1 University, EMR 3738, Oullins, France.
AD  - Department of Statistics unit, Hospices Civils de Lyon, Pierre-Benite, France.
AD  - CNRS, UMR 5558 Biometry and Evolutionary Biology Laboratory, Universite Lyon 1, 
      Villeurbanne, France.
LA  - eng
PT  - Journal Article
PT  - Systematic Review
DEP - 20190204
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Antineoplastic Agents, Immunological/*adverse effects
MH  - B7-H1 Antigen/*antagonists & inhibitors
MH  - CTLA-4 Antigen/*antagonists & inhibitors
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/etiology
MH  - Humans
MH  - Programmed Cell Death 1 Receptor/*antagonists & inhibitors
MH  - Randomized Controlled Trials as Topic
OTO - NOTNLM
OT  - adverse event
OT  - immune checkpoint inhibitors
OT  - immune toxicity
OT  - quality control
OT  - systematic review
EDAT- 2019/01/18 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/01/18 06:00
PHST- 2018/09/04 00:00 [received]
PHST- 2018/12/02 00:00 [revised]
PHST- 2019/01/02 00:00 [accepted]
PHST- 2019/01/18 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/01/18 06:00 [entrez]
AID - 10.1002/ijc.32132 [doi]
PST - ppublish
SO  - Int J Cancer. 2019 Aug 1;145(3):639-648. doi: 10.1002/ijc.32132. Epub 2019 Feb 4.