PMID- 38089086
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231213
IS  - 2770-9183 (Electronic)
IS  - 2770-9191 (Print)
IS  - 2770-9183 (Linking)
VI  - 1
IP  - 4
DP  - 2022 Dec
TI  - Deaths and adverse events from adjuvant therapy with immune checkpoint inhibitors 
      in solid malignant tumors: A systematic review and network meta-analysis.
PG  - 293-304
LID - 10.1002/cai2.34 [doi]
AB  - BACKGROUND: By prolonging overall survival and reducing disease recurrence rates, 
      immune checkpoint inhibitors (ICIs) are an emerging adjuvant therapy option for 
      patients with resectable malignant tumors. However, the safety profile (deaths 
      and adverse events [AEs]) of adjuvant ICIs has not been fully described. METHODS: 
      We searched the literature for phase III randomized clinical trials that compared 
      PD-1, PD-L1, and CTLA-4 inhibitors in solid malignant tumors. Incidences of 
      death, discontinuation, AEs of any cause, treatment-related adverse events 
      (TRAEs), and immune-related adverse events (IRAEs) were extracted for the network 
      meta-analysis. Network meta-analyses with low incidence and poor convergence are 
      reported as incidences with 95% confidence intervals (95% CIs). RESULTS: Ten 
      randomized clinical trials that included 9243 patients who received ICI adjuvant 
      therapy were eligible. In total, 21 deaths due to TRAEs were recorded, with an 
      overall incidence of 0.40% (95% CI: 0.26-0.61). The treatment-related mortality 
      rates for ipilimumab (0.76%, 95% CI: 0.31-1.55) and atezolizumab (0.56%, 95% CI: 
      0.18-1.31) were higher than for pembrolizumab (0.24%, 95% CI: 0.10-0.56) and 
      nivolumab (0.30%, 95% CI: 0.08-0.77). The most frequent causes of death were 
      associated with the gastrointestinal (0.10%, 95% CI: 0.04-0.24) and pulmonary 
      (0.08%, 95% CI: 0.03-0.21) systems. Compared with the control arm, we found that 
      nivolumab (odds ratio [OR]: 2.73, 95% CI: 0.49-15.85) and atezolizumab (OR: 
      12.43, 95% CI: 2.42-78.48) caused the fewest grade >/=3 TRAEs and IRAEs. Commonly 
      reported IRAEs of special interest were analyzed, and two agents were found to 
      have IRAEs with incidences >10%, i.e., hepatitis for atezolizumab (14.80%, 95% 
      CI: 12.53-17.32) and hypophysitis for ipilimumab (13.53%, 95% CI: 11.38-15.90). 
      CONCLUSIONS: Ipilimumab and atezolizumab were correlated with higher 
      treatment-related death rates than pembrolizumab and nivolumab, in which the 
      gastrointestinal and pulmonary systems were mostly involved. Regarding severe 
      TRAEs and IRAEs, nivolumab and atezolizumab are likely to be the safest agent, 
      respectively. This study will guide clinical practice for ICI adjuvant therapies.
CI  - (c) 2022 The Authors. Cancer Innovation published by John Wiley & Sons Ltd. on 
      behalf of Tsinghua University Press.
FAU - Xie, Ruiyang
AU  - Xie R
AD  - Department of Urology, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union 
      Medical College Beijing China.
FAU - Wu, Jie
AU  - Wu J
AD  - Department of Urology, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union 
      Medical College Beijing China.
FAU - Shang, Bingqing
AU  - Shang B
AD  - Department of Urology, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union 
      Medical College Beijing China.
FAU - Bi, Xingang
AU  - Bi X
AD  - Department of Urology, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union 
      Medical College Beijing China.
FAU - Cao, Chuanzhen
AU  - Cao C
AD  - Department of Urology, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union 
      Medical College Beijing China.
FAU - Guan, Youyan
AU  - Guan Y
AD  - Department of Urology, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union 
      Medical College Beijing China.
FAU - Shi, Hongzhe
AU  - Shi H
AD  - Department of Urology, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union 
      Medical College Beijing China.
FAU - Shou, Jianzhong
AU  - Shou J
AUID- ORCID: 0000-0002-1148-2442
AD  - Department of Urology, National Cancer Center/National Clinical Research Center 
      for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union 
      Medical College Beijing China.
LA  - eng
PT  - Journal Article
DEP - 20221114
PL  - England
TA  - Cancer Innov
JT  - Cancer innovation
JID - 9918713888606676
PMC - PMC10686117
OTO - NOTNLM
OT  - adjuvant therapy
OT  - adverse event
OT  - cancer
OT  - death
OT  - immune checkpoint inhibitor
COIS- The authors declare no conflict of interest.
EDAT- 2023/12/13 18:42
MHDA- 2023/12/13 18:43
PMCR- 2022/11/14
CRDT- 2023/12/13 12:47
PHST- 2022/08/10 00:00 [received]
PHST- 2022/09/13 00:00 [revised]
PHST- 2022/09/28 00:00 [accepted]
PHST- 2023/12/13 18:43 [medline]
PHST- 2023/12/13 18:42 [pubmed]
PHST- 2023/12/13 12:47 [entrez]
PHST- 2022/11/14 00:00 [pmc-release]
AID - CAI234 [pii]
AID - 10.1002/cai2.34 [doi]
PST - epublish
SO  - Cancer Innov. 2022 Nov 14;1(4):293-304. doi: 10.1002/cai2.34. eCollection 2022 
      Dec.