PMID- 36200429
OWN - NLM
STAT- MEDLINE
DCOM- 20221110
LR  - 20230111
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Print)
IS  - 0269-4727 (Linking)
VI  - 47
IP  - 11
DP  - 2022 Nov
TI  - Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study.
PG  - 1837-1844
LID - 10.1111/jcpt.13777 [doi]
AB  - WHAT IS KNOWN AND OBJECTIVE: This study aimed to explore the safety profile of 
      trastuzumab deruxtecan (T-DXd, formerly DS-8201a) using multi-source medical 
      data. METHODS: We explored trastuzumab deruxtecan related adverse events (AEs) in 
      clinical trials available in ClinicalTrials.gov and electronic databases 
      (MEDLINE, EMBASE and PubMed) up to July 16, 2022. Meta-analysis was performed by 
      using incidence rate with 95%CIs. In the pharmacovigilance study of FDA Adverse 
      Event Reporting System (FAERS), the reporting odds ratio (ROR) and the medicines 
      and healthcare products regulatory agency (MHRA) methods were used to analyse the 
      real-world AEs (up to June 28, 2022). RESULTS AND DISCUSSION: A 8 clinical trials 
      enrolled 1457 patients were included. The most common AEs of any grade were 
      gastrointestinal disorders and blood and lymphatic system disorders. The most 
      common AE of grade 3 or higher was neutropenia (21.4%, 95%CI: 14.7%-28.1%, I(2) 
       = 91%). The incidence of interstitial lung disease (ILD) and decreased left 
      ventricular ejection fraction were 10.9% (95%CI: 7.2%-14.5%, I(2)  = 82%) and 
      1.2% (95%CI: 0.7%-2.2%, I(2)  = 98%), respectively. A total of 1244 AE reports 
      were identified in the pharmacovigilance study. Gastrointestinal toxicity 
      (ROR = 21.65), myelosuppression (ROR = 36.88), interstitial lung disease 
      (ROR = 50.30), pneumonitis (ROR = 36.59), decreased ejection fraction 
      (ROR = 16.08), and taste disorder (ROR = 14.06) mentioned in the instructions 
      showed strong signals. Also, ascites (ROR = 14.90), lung opacity (ROR = 78.80), 
      pulmonary fibrosis (ROR = 5.59), and increased KL-6 (ROR = 1761.97), which were 
      not mentioned in the instructions, showed strong signals. WHAT IS NEW AND 
      CONCLUSION: Trastuzumab deruxtecan was well tolerated, and more attention should 
      be paid on ILD as well as decreased ejection fraction.
CI  - (c) 2022 The Authors. Journal of Clinical Pharmacy and Therapeutics published by 
      John Wiley & Sons Ltd.
FAU - Guo, Zihan
AU  - Guo Z
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Ding, Yunlan
AU  - Ding Y
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Wang, Mengmeng
AU  - Wang M
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Liu, Jiyong
AU  - Liu J
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Zhai, Qing
AU  - Zhai Q
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Du, Qiong
AU  - Du Q
AUID- ORCID: 0000-0003-4830-9704
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
LA  - eng
GR  - SHWRS (2020)087/Shanghai "Rising Stars of Medical Talent" Youth Development 
      Program Youth Medical Talents Clinical Pharmacist Program/
GR  - SHDC2020CR3085B/Clinical Research Plan of SHDC/
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20221006
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 5384HK7574 (trastuzumab deruxtecan)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Humans
MH  - *Pharmacovigilance
MH  - Stroke Volume
MH  - Ventricular Function, Left
MH  - Trastuzumab/adverse effects
MH  - *Lung Diseases, Interstitial
PMC - PMC9827941
OTO - NOTNLM
OT  - adverse event
OT  - meta-analysis
OT  - pharmacovigilance
OT  - real-world
OT  - trastuzumab deruxtecan
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2022/10/07 06:00
MHDA- 2022/11/11 06:00
PMCR- 2023/01/09
CRDT- 2022/10/06 04:52
PHST- 2022/08/31 00:00 [received]
PHST- 2022/09/04 00:00 [accepted]
PHST- 2022/10/07 06:00 [pubmed]
PHST- 2022/11/11 06:00 [medline]
PHST- 2022/10/06 04:52 [entrez]
PHST- 2023/01/09 00:00 [pmc-release]
AID - JCPT13777 [pii]
AID - 10.1111/jcpt.13777 [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2022 Nov;47(11):1837-1844. doi: 10.1111/jcpt.13777. Epub 2022 
      Oct 6.