PMID- 31708783
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - The Differences in the Safety and Tolerability of Immune Checkpoint Inhibitors as 
      Treatment for Non-Small Cell Lung Cancer and Melanoma: Network Meta-Analysis and 
      Systematic Review.
PG  - 1260
LID - 10.3389/fphar.2019.01260 [doi]
LID - 1260
AB  - Background: Immune checkpoint inhibitors (ICIs) have evolved for the treatment of 
      solid tumors. In addition to the efficacy of ICIs for cancer, the adverse events 
      (AEs) of ICIs are also noteworthy for gradually more extensive clinical use. 
      Objective: To conduct a systematic review and network meta-analysis to evaluate 
      the treatment-related AEs that occurred in clinical trials using different kinds 
      of ICIs, to explore the differences in AEs among ICIs for treating non-small cell 
      lung cancer (NSCLC) and melanoma, and to compare select immune-related AEs. 
      Methods: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and other 
      available sources were systematically searched for published reports up to 
      January 1, 2019. Two reviewers independently selected reports about phase II/III 
      randomized controlled trials to compare among ICIs and between ICIs and 
      chemotherapy. After the bias assessment of all included trials, a Bayesian 
      network meta-analysis was performed. The primary outcomes were any-grade and 
      high-grade treatment-related AEs from all ICIs. The secondary outcomes were AEs 
      in patients with NSCLC and melanoma and the presence of the select AEs 
      pneumonitis/pneumonia and colitis. Results: Eighteen randomized controlled trials 
      containing 11,223 patients with NSCLC or melanoma were included. A total network 
      meta-analysis was conducted. The meta-analysis showed that atezolizumab 1,200 mg 
      and pembrolizumab 2 mg/kg every 3 weeks were generally more tolerable than other 
      ICIs. ICI combined with chemotherapy might suggest a higher risk of 
      treatment-related AEs than monotherapy with a single ICI, except durvalumab and 
      ipilimumab. In the NSCLC subgroup, pembrolizumab was associated with a higher 
      risk of high-grade AEs than nivolumab. In addition, ICIs (nivolumab, 
      atezolizumab, and avelumab) led to a lower risk of any/high-grade 
      treatment-related AEs than traditional chemotherapy and ICI combination 
      chemotherapy. However, ICIs did not present preferable safety and tolerability 
      compared to chemotherapy in treating melanoma. Compared with chemotherapy, 
      nivolumab, durvalumab, two ICIs, and ICI combined chemotherapy led to more 
      pneumonitis/pneumonia. However, when treating NSCLC, different types of ICIs did 
      not differ significantly regarding the incidence of pneumonitis/pneumonia. A 
      combination of nivolumab and ipilimumab had the highest risk for colitis, while 
      pembrolizumab and atezolizumab had a lower possibility than the other ICIs. 
      Conclusion: Atezolizumab 1,200 mg and pembrolizumab 2 mg/kg every 3 weeks were 
      ordinarily safer than other ICIs. When treating NSCLC, nivolumab had the lowest 
      risk; when treating melanoma, pembrolizumab had the lowest toxicity.
CI  - Copyright (c) 2019 Chai, Du, Zhu and Wu.
FAU - Chai, Qing-Qing
AU  - Chai QQ
AD  - Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 
      Shanghai, China.
FAU - Du, Jiang-Yang
AU  - Du JY
AD  - Medical Decision and Economic Group, Department of Pharmacy, Ren Ji Hospital, 
      School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
FAU - Zhu, Jun
AU  - Zhu J
AD  - Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 
      Shanghai, China.
FAU - Wu, Bin
AU  - Wu B
AD  - Medical Decision and Economic Group, Department of Pharmacy, Ren Ji Hospital, 
      School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
LA  - eng
PT  - Systematic Review
DEP - 20191024
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6821878
OTO - NOTNLM
OT  - immune checkpoint inhibitors
OT  - melanoma
OT  - network meta-analysis
OT  - non-small cell lung cancer
OT  - treatment-related adverse events
EDAT- 2019/11/12 06:00
MHDA- 2019/11/12 06:01
PMCR- 2019/10/24
CRDT- 2019/11/12 06:00
PHST- 2019/04/25 00:00 [received]
PHST- 2019/09/30 00:00 [accepted]
PHST- 2019/11/12 06:00 [entrez]
PHST- 2019/11/12 06:00 [pubmed]
PHST- 2019/11/12 06:01 [medline]
PHST- 2019/10/24 00:00 [pmc-release]
AID - 10.3389/fphar.2019.01260 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Oct 24;10:1260. doi: 10.3389/fphar.2019.01260. eCollection 
      2019.