PMID- 35219113
OWN - NLM
STAT- MEDLINE
DCOM- 20220315
LR  - 20220315
IS  - 1532-3080 (Electronic)
IS  - 0960-9776 (Print)
IS  - 0960-9776 (Linking)
VI  - 62
DP  - 2022 Apr
TI  - Interstitial lung disease in patients treated with Cyclin-Dependent Kinase 4/6 
      inhibitors: A systematic review and meta-analysis of randomized controlled 
      trials.
PG  - 162-169
LID - S0960-9776(22)00038-8 [pii]
LID - 10.1016/j.breast.2022.02.011 [doi]
AB  - BACKGROUND: Cyclin-Dependent Kinase (CDK) 4/6 inhibitors have shown significant 
      clinical activity in cancer patients. However, some concerns regarding rare 
      adverse events (AEs) have occurred including interstitial lung disease 
      (ILD)/pneumonitis, for which data are deficient. The aim of this study was to 
      evaluate the overall incidence and risk of ILD/pneumonitis related to CDK4/6 
      inhibitors in randomized controlled trials (RCTs). METHODS: Electronic databases 
      and ClinicalTrials.gov were searched from inception to October 1, 2021 for RCTs 
      reporting the occurrence of LD/pneumonitis in cancer patients treated with CDK4/6 
      inhibitors. Peto odds ratios (Peto ORs) and 95% confidence intervals (CIs) were 
      used to pool the study. RESULTS: 12 RCTs with a total of 16,060 patients were 
      eligible. The overall incidence of all-grade ILD/pneumonitis was 1.6% (131/8407) 
      in the treatment group compared with 0.7% (50/7349) in the control group. CDK4/6 
      inhibitors significantly increased the risk of all-grade ILD/pneumonitis with a 
      pooled Peto OR of 2.12 (95% CI [1.57, 2.86], P < 0.00001) with no heterogeneity 
      (I(2) = 0%, chi(2) P = 0.98). A higher incidence of grade 3 or higher 
      ILD/pneumonitis was also observed in the treatment group (0.2%, 16/7087) compared 
      with the control group (0.05%, 3/6617) with a Peto OR of 3.22 (95% CI [1.28, 
      8.09], P = 0.01) with no heterogeneity (I(2) = 0%, chi(2) P = 0.62). Two grade 5 
      pneumonitis were reported in the included studies. Subgroup analyses did not show 
      any significant difference. CONCLUSIONS: The risk of all-grade and grade 3 or 
      higher ILD/pneumonitis was higher in patients treated with CDK4/6 inhibitors 
      compared to controls. The awareness for these rare AEs in the application of 
      CDK4/6 inhibitors should be enhanced. Further studies are required to validate 
      the mechanisms and the risk factors of ILD/pneumonitis with CDK4/6 inhibitors.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, No 
      8, Gongren Tiyuchang South Road, Chaoyang District, Beijing, China; Department of 
      Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 
      No.17, Qi He Lou Street, Dongcheng District, Beijing, China.
FAU - Ma, Zhuo
AU  - Ma Z
AD  - Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, No 
      8, Gongren Tiyuchang South Road, Chaoyang District, Beijing, China.
FAU - Sun, Ximu
AU  - Sun X
AD  - Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital 
      Medical University, No.17, Qi He Lou Street, Dongcheng District, Beijing, China.
FAU - Feng, Xin
AU  - Feng X
AD  - Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital 
      Medical University, No.17, Qi He Lou Street, Dongcheng District, Beijing, China. 
      Electronic address: fengxin1115@126.com.
FAU - An, Zhuoling
AU  - An Z
AD  - Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, No 
      8, Gongren Tiyuchang South Road, Chaoyang District, Beijing, China. Electronic 
      address: anzhuoling@163.com.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20220222
PL  - Netherlands
TA  - Breast
JT  - Breast (Edinburgh, Scotland)
JID - 9213011
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
SB  - IM
MH  - *Breast Neoplasms
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinase 6
MH  - Female
MH  - Humans
MH  - Incidence
MH  - *Lung Diseases, Interstitial/chemically induced/epidemiology
MH  - Randomized Controlled Trials as Topic
PMC - PMC8873944
OTO - NOTNLM
OT  - Cyclin-dependent kinase (CDK) 4/6 inhibitors
OT  - ILD
OT  - Meta-analysis
OT  - Pneumonitis
OT  - Randomized controlled trials
COIS- All authors have no significant disclosures.
EDAT- 2022/02/27 06:00
MHDA- 2022/03/16 06:00
PMCR- 2022/02/22
CRDT- 2022/02/26 20:14
PHST- 2021/11/18 00:00 [received]
PHST- 2022/02/17 00:00 [revised]
PHST- 2022/02/20 00:00 [accepted]
PHST- 2022/02/27 06:00 [pubmed]
PHST- 2022/03/16 06:00 [medline]
PHST- 2022/02/26 20:14 [entrez]
PHST- 2022/02/22 00:00 [pmc-release]
AID - S0960-9776(22)00038-8 [pii]
AID - 10.1016/j.breast.2022.02.011 [doi]
PST - ppublish
SO  - Breast. 2022 Apr;62:162-169. doi: 10.1016/j.breast.2022.02.011. Epub 2022 Feb 22.