PMID- 34925331
OWN - NLM
STAT- MEDLINE
DCOM- 20220217
LR  - 20220217
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in 
      Advanced Lung Cancer.
PG  - 760737
LID - 10.3389/fimmu.2021.760737 [doi]
LID - 760737
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs) have become one of the standard 
      treatment options for advanced lung cancer. However, adverse events (AEs), 
      particularly immune-related AEs (irAEs), caused by these drugs have aroused 
      public attention. The current network meta-analysis (NMA) aimed to compare the 
      risk of AEs across different ICI-based regimens in patients with advanced lung 
      cancer. METHODS: We systematically searched the PubMed, EMBASE, and Cochrane 
      Library databases (from inception to 19 April 2021) for relevant randomized 
      controlled trials (RCTs) that compared two or more treatments, with at least one 
      ICI administered to patients with advanced lung cancer. The primary outcomes were 
      treatment-related AEs and irAEs, including grade 1-5 and grade 3-5. The secondary 
      outcomes were grade 1-5 and grade 3-5 irAEs in specific organs. Both pairwise and 
      network meta-analyses were conducted for chemotherapy, ICI monotherapy, ICI 
      monotherapy + chemotherapy, dual ICIs therapy, and dual ICIs + chemotherapy for 
      all safety outcomes. Node-splitting analyses were performed to test 
      inconsistencies in network. Sensitivity analyses were adopted by restricting 
      phase III RCTs and studies that enrolled patients with non-small cell lung 
      cancer. RESULTS: Overall, 38 RCTs involving 22,178 patients with advanced lung 
      cancer were enrolled. Both pooled incidence and NMA indicated that treatments 
      containing chemotherapy increased the risk of treatment-related AEs when compared 
      with ICI-based regimens without chemotherapy. As for grade 1-5 irAEs, dual ICIs + 
      chemotherapy was associated with the highest risk of irAEs (probability in 
      ranking first: 50.5%), followed by dual-ICI therapy (probability in ranking 
      second: 47.2%), ICI monotherapy (probability in ranking third: 80.0%), ICI 
      monotherapy + chemotherapy (probability in ranking fourth: 98.0%), and finally 
      chemotherapy (probability in ranking fifth: 100.0%). In grade 3-5 irAEs, subtle 
      differences were observed; when ranked from least safe to safest, the trend was 
      dual ICIs therapy (60.4%), dual ICIs + chemotherapy (42.5%), ICI monotherapy 
      (76.3%), ICI monotherapy + chemotherapy (95.0%), and chemotherapy (100.0%). 
      Furthermore, detailed comparisons between ICI-based options provided irAE 
      profiles based on specific organ/system and severity. CONCLUSIONS: In 
      consideration of overall immune-related safety profiles, ICI monotherapy + 
      chemotherapy might be a better choice among ICI-based treatments for advanced 
      lung cancer. The safety profiles of ICI-based treatments are various by specific 
      irAEs and their severity. SYSTEMATIC REVIEW REGISTRATION: 
      https://www.crd.york.ac.uk/prospero, identifier CRD42021268650.
CI  - Copyright (c) 2021 Yan, Cui, Fu, Su, Chen, Gu and Lin.
FAU - Yan, Yi-Dan
AU  - Yan YD
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Cui, Jiu-Jie
AU  - Cui JJ
AD  - Department of Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Fu, Jie
AU  - Fu J
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Su, Ying-Jie
AU  - Su YJ
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Chen, Xiao-Yu
AU  - Chen XY
AD  - Department of Pharmacy, The People's Hospital of Guangxi Zhuang Autonomous Region 
      (Guangxi Academy of Medical Sciences), Nanning, China.
FAU - Gu, Zhi-Chun
AU  - Gu ZC
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Lin, Hou-Wen
AU  - Lin HW
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
LA  - eng
PT  - Comparative Study
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20211203
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Humans
MH  - Immune Checkpoint Inhibitors/*adverse effects
MH  - Lung Neoplasms/*drug therapy
MH  - Network Meta-Analysis
MH  - Randomized Controlled Trials as Topic
PMC - PMC8677695
OTO - NOTNLM
OT  - adverse events
OT  - immune checkpoint inhibitors
OT  - lung cancer
OT  - network comparison
OT  - safety
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/12/21 06:00
MHDA- 2022/02/19 06:00
PMCR- 2021/01/01
CRDT- 2021/12/20 06:06
PHST- 2021/08/18 00:00 [received]
PHST- 2021/11/16 00:00 [accepted]
PHST- 2021/12/20 06:06 [entrez]
PHST- 2021/12/21 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.760737 [doi]
PST - epublish
SO  - Front Immunol. 2021 Dec 3;12:760737. doi: 10.3389/fimmu.2021.760737. eCollection 
      2021.