PMID- 34295666
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220425
IS  - 2218-6751 (Print)
IS  - 2226-4477 (Electronic)
IS  - 2218-6751 (Linking)
VI  - 10
IP  - 6
DP  - 2021 Jun
TI  - Immune-related adverse event profile of combination treatment of PD-(L)1 
      checkpoint inhibitors and bevacizumab in non-small cell lung cancer patients: 
      data from the FDA adverse event reporting system.
PG  - 2614-2624
LID - 10.21037/tlcr-21-464 [doi]
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs) and bevacizumab-based therapy are 
      a promising treatment approach to significantly improving overall survival (OS) 
      of non-small cell lung cancer (NSCLC) patients. However, the incidence of adverse 
      events induced by a combination treatment with programmed cell death-1 or 
      programmed death ligand 1 [PD-(L)1] inhibitor and bevacizumab remains unknown. 
      The current evidence from prospective studies is limited. Thus, efforts using 
      real-world data to further improve our understanding of the potential adverse 
      events will be necessary. METHODS: The present study included 15,872 participants 
      with NSCLC in the FDA Adverse Event Reporting System (FAERS) database from April 
      2013 to September 2019. The definition of adverse events (AEs) relied on the 
      Medical Dictionary for Regulatory Activities (MedDRA). Statistical analysis was 
      performed, and odds ratio (ORs) with 95% confidence intervals (CIs) were 
      calculated. RESULTS: Of the 15,872 participants with NSCLC, 15,463 cases were 
      treated with the PD-(L)1 inhibitor monotherapy, while 409 cases were treated with 
      both PD-(L)1 inhibitor and bevacizumab. Compared with monotherapy, combination 
      therapy had lower risks of pneumonitis, respiratory failure, edema, disease 
      progression, and death; however, combination therapy was also associated with 
      significantly higher risks of pyrexia, general physical health deterioration, 
      stomatitis, dehydration, thrombocytopenia, peripheral neuropathy, nephritis, bone 
      marrow failure, immune thrombocytopenic purpura, neutropenia, and serious AEs. 
      The results of the multivariate analysis suggested that combination therapy was 
      the independent risk factor for pyrexia, neutropenia, nephritis, ITP, and the 
      independent protective factor for respiratory failure. CONCLUSIONS: We observed 
      that the spectrum and risk of irAEs differed widely between therapeutic regimens, 
      and irAEs involved multiple organ systems both in monotherapy or combination 
      therapy. Deepening our understanding of irAEs has a great clinical value for 
      improving individualized clinical patient management and the safety of medication 
      use.
CI  - 2021 Translational Lung Cancer Research. All rights reserved.
FAU - Bai, Shuai
AU  - Bai S
AD  - Department of Oncology, The First Affiliated Hospital of Shandong First Medical 
      University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
AD  - Shandong Lung Cancer Institute, Jinan, China.
FAU - Tian, Tiantian
AU  - Tian T
AD  - Department of Oncology, The First Affiliated Hospital of Shandong First Medical 
      University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
AD  - Shandong Lung Cancer Institute, Jinan, China.
FAU - Pacheco, Jose M
AU  - Pacheco JM
AD  - Division of Medical Oncology, Department of Internal Medicine, University of 
      Colorado Cancer Center, Aurora, CO, USA.
FAU - Tachihara, Motoko
AU  - Tachihara M
AD  - Division of Respiratory Medicine, Department of Internal Medicine, Kobe 
      University Graduate School of Medicine, Kobe, Japan.
FAU - Hu, Pingping
AU  - Hu P
AD  - Department of Oncology, The First Affiliated Hospital of Shandong First Medical 
      University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
AD  - Shandong Lung Cancer Institute, Jinan, China.
FAU - Zhang, Jiandong
AU  - Zhang J
AD  - Department of Oncology, The First Affiliated Hospital of Shandong First Medical 
      University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
AD  - Shandong Lung Cancer Institute, Jinan, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Lung Cancer Res
JT  - Translational lung cancer research
JID - 101646875
PMC - PMC8264309
OTO - NOTNLM
OT  - Immune-related adverse events (irAEs)
OT  - PD-1
OT  - PD-L1
OT  - bevacizumab
OT  - non-small cell lung cancer (NSCLC)
COIS- Conflict of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/tlcr-21-464). The authors declare 
      that this work was supported by the National Natural Science Foundation of China 
      (No. 81672974, 81602719, and 81803043), and that the research was conducted in 
      the absence of any commercial or financial relationships that could be construed 
      as a potential conflict of interest. The authors have no other conflicts of 
      interest to declare.
EDAT- 2021/07/24 06:00
MHDA- 2021/07/24 06:01
PMCR- 2021/06/01
CRDT- 2021/07/23 06:50
PHST- 2021/03/22 00:00 [received]
PHST- 2021/06/23 00:00 [accepted]
PHST- 2021/07/23 06:50 [entrez]
PHST- 2021/07/24 06:00 [pubmed]
PHST- 2021/07/24 06:01 [medline]
PHST- 2021/06/01 00:00 [pmc-release]
AID - tlcr-10-06-2614 [pii]
AID - 10.21037/tlcr-21-464 [doi]
PST - ppublish
SO  - Transl Lung Cancer Res. 2021 Jun;10(6):2614-2624. doi: 10.21037/tlcr-21-464.