PMID- 32934874
OWN - NLM
STAT- MEDLINE
DCOM- 20210714
LR  - 20240330
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 9
IP  - 1
DP  - 2020 May 21
TI  - Dose dependence of treatment-related adverse events for immune checkpoint 
      inhibitor therapies: a model-based meta-analysis.
PG  - 1748982
LID - 10.1080/2162402X.2020.1748982 [doi]
LID - 1748982
AB  - Programmed cell death-1 (PD-1) and/or cytotoxic T lymphocyte-associated antigen 4 
      (CTLA-4) immune checkpoint inhibitor (ICI) treatments are associated with adverse 
      events (AEs), which may be dependent on ICI dose. Applying a model-based 
      meta-analysis to evaluate safety data from published clinical trials from 2005 to 
      2018, we analyzed the dose/exposure dependence of ICI treatment-related AE (trAE) 
      and immune-mediated AE (imAE) rates. Unlike with PD-1 inhibitor monotherapy, 
      CTLA-4 inhibitor monotherapy exhibited a dose/exposure dependence on most AE 
      types evaluated. Furthermore, combination therapy with PD-1 inhibitor 
      significantly strengthened the dependence of trAE and imAE rates on CTLA-4 
      inhibitor dose/exposure.
CI  - (c) 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
FAU - Shulgin, Boris
AU  - Shulgin B
AD  - M&S Decisions LLC, Moscow, Russia.
FAU - Kosinsky, Yuri
AU  - Kosinsky Y
AD  - M&S Decisions LLC, Moscow, Russia.
FAU - Omelchenko, Andrey
AU  - Omelchenko A
AD  - M&S Decisions LLC, Moscow, Russia.
FAU - Chu, Lulu
AU  - Chu L
AD  - PK Sciences Modeling & Simulation, Novartis Institutes of BioMedical Research, 
      Cambridge, MA, USA.
FAU - Mugundu, Ganesh
AU  - Mugundu G
AD  - Clinical Pharmacology & Quantitative Pharmacology, R&D BioPharmaceuticals, 
      AstraZeneca, Waltham, MA, USA.
FAU - Aksenov, Sergey
AU  - Aksenov S
AD  - Clinical Pharmacology & Quantitative Pharmacology, R&D BioPharmaceuticals, 
      AstraZeneca, Waltham, MA, USA.
FAU - Pimentel, Rodrigo
AU  - Pimentel R
AD  - Medical Affairs, AstraZeneca, Gaithersburg, MD, USA.
FAU - DeYulia, Garrett
AU  - DeYulia G
AD  - Medical Affairs, AstraZeneca, Gaithersburg, MD, USA.
FAU - Kim, Geoffrey
AU  - Kim G
AD  - Applied Innovation, BeiGene, Cambridge, MA, USA.
FAU - Peskov, Kirill
AU  - Peskov K
AUID- ORCID: 0000-0003-0678-5729
AD  - M&S Decisions LLC, Moscow, Russia.
AD  - I.M.Sechenov first Moscow State Medical University of the Russian Ministry of 
      Health, Moscow, Russia.
FAU - Helmlinger, Gabriel
AU  - Helmlinger G
AUID- ORCID: 0000-0003-4925-2463
AD  - Clinical Pharmacology & Toxicology, Obsidian Therapeutics, Cambridge, MA, USA.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200521
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Immune Checkpoint Inhibitors)
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects
MH  - B7-H1 Antigen/antagonists & inhibitors
MH  - CTLA-4 Antigen/antagonists & inhibitors
MH  - Clinical Trials as Topic
MH  - Combined Modality Therapy
MH  - Dose-Response Relationship, Immunologic
MH  - Humans
MH  - *Immune Checkpoint Inhibitors/administration & dosage/adverse effects
MH  - *Neoplasms/immunology/therapy
PMC - PMC7466858
OTO - NOTNLM
OT  - Adverse events
OT  - immune checkpoint inhibitor
OT  - meta-analysis
COIS- BS, YK, AO, and KP are employees of M&S Decisions LLC, Moscow, Russia, which 
      received funding from AstraZeneca to conduct this research and analysis; LC, GM, 
      SA, RP, GD, GK, and GH are all employees of AstraZeneca.
EDAT- 2020/09/17 06:00
MHDA- 2020/09/17 06:01
PMCR- 2020/05/21
CRDT- 2020/09/16 05:39
PHST- 2020/09/16 05:39 [entrez]
PHST- 2020/09/17 06:00 [pubmed]
PHST- 2020/09/17 06:01 [medline]
PHST- 2020/05/21 00:00 [pmc-release]
AID - 1748982 [pii]
AID - 10.1080/2162402X.2020.1748982 [doi]
PST - epublish
SO  - Oncoimmunology. 2020 May 21;9(1):1748982. doi: 10.1080/2162402X.2020.1748982.