PMID- 38327983
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 15
DP  - 2024
TI  - Comparing the difference of adverse events with HER2 inhibitors: a study of the 
      FDA adverse event reporting system (FAERS).
PG  - 1288362
LID - 10.3389/fphar.2024.1288362 [doi]
LID - 1288362
AB  - Aim and background: This study attempted to identify similarities and differences 
      in adverse events (AEs) between human epidermal growth factor receptor 2 (HER2) 
      inhibitors, especially those related to hemorrhagic events and nervous system 
      disorders. Methods: This study summarized the types, frequencies, and system 
      organ classes (SOCs) of AEs of HER2 inhibitors. The US Food and Drug 
      Administration Adverse Event Reporting System (FAERS) data from January 2004 
      through March 2022 was collected and analyzed. Disproportionality analyses were 
      conducted to detect AEs signals for every HER2 inhibitor. The chi-square test, 
      Wilcoxon test, and descriptive analysis were used to compare the differences of 
      AEs for specific SOCs or drugs. Results: A total of 47,899 AE reports were 
      obtained for eight HER2 inhibitors. Trastuzumab-related AEs were reported in the 
      highest number and combination of regimens. In monotherapy, trastuzumab had the 
      highest reported rate of cardiac disorders-related AEs (24.0%). However, 
      small-molecule drugs exceeded other drugs in the reported rates of AEs related to 
      gastrointestinal disorders, metabolism and nutrition disorders. The highest 
      reported rates of respiratory disorders (47.3%) and hematologic disorders (22.4%) 
      were associated with treatment with trastuzumab deruxtecan (T-DXd). Patients 
      treated with trastuzumab emtansine (TDM-1) had the highest reported rate (7.28%) 
      of hemorrhagic events, especially intracranial haemorrhage events. In addition, 
      patients treated with TDM-1 with concomitant thrombocytopenia were likely to 
      experience hemorrhagic events compared to other HER2 inhibitors (p < 0.001). The 
      median time to onset of intracranial haemorrhage associated with trastuzumab 
      (0.5 months) and TDM-1 (0.75 months) was short. However, there was no significant 
      difference in median time to onset intracranial haemorrhage between patients in 
      different age groups or with different outcomes. Disproportionality analysis 
      results reveal that cerebral haemorrhage is a positive signal associated with 
      T-DXd and TDM-1. In addition, tucatinib was the drug with the highest rate of 
      reported nervous system disorders (31.38%). Memory impairment (83 cases) is a 
      positive signal for tucatinib. Conclusion: The types and reporting rates of AEs 
      associated with different HER2 inhibitors vary across multiple systems. In 
      addition, hemorrhagic events concomitant with TDM-1 treatment and nervous system 
      disorders concomitant with tucatinib treatment may be worthy of attention.
CI  - Copyright (c) 2024 Bao, Chen, Duan, Wang, Lai, Mo and Zhu.
FAU - Bao, Yiwen
AU  - Bao Y
AD  - Department of Oncology, The People's Hospital of Qiannan, Duyun, Guizhou, China.
AD  - Department of Oncology, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Chen, Jiaju
AU  - Chen J
AD  - Gastrointestinal Surgery, The Affiliated Hospital of Guizhou Medical University, 
      Guiyang, Guizhou, China.
FAU - Duan, Luting
AU  - Duan L
AD  - Department of Cardiovascular Medicine, The People's Hospital of Qiannan, Duyun, 
      Guizhou, China.
FAU - Wang, Fujue
AU  - Wang F
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, 
      Sichuan University and Collaborative Innovation Center, Chengdu, China.
FAU - Lai, Han
AU  - Lai H
AD  - Department of Oncology, The People's Hospital of Qiannan, Duyun, Guizhou, China.
FAU - Mo, Zeming
AU  - Mo Z
AD  - Department of Oncology, The People's Hospital of Qiannan, Duyun, Guizhou, China.
AD  - Division of Head and Neck Tumor Multimodality Treatment, Cancer Center, West 
      China Hospital, Sichuan University, Chengdu, China.
FAU - Zhu, Weiliang
AU  - Zhu W
AD  - Department of Oncology, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20240124
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10847310
OTO - NOTNLM
OT  - FAERS database
OT  - HER2 inhibitors
OT  - TDM-1
OT  - Tucatinib
OT  - adverse drug events
OT  - hemorrhagic events
OT  - nervous system disorders
COIS- The authors declare 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 reviewer LZ declared a shared parent affiliation with 
      the author ZM to the handling editor at the time of review.
EDAT- 2024/02/08 06:42
MHDA- 2024/02/08 06:43
PMCR- 2024/01/24
CRDT- 2024/02/08 04:13
PHST- 2023/09/04 00:00 [received]
PHST- 2024/01/08 00:00 [accepted]
PHST- 2024/02/08 06:43 [medline]
PHST- 2024/02/08 06:42 [pubmed]
PHST- 2024/02/08 04:13 [entrez]
PHST- 2024/01/24 00:00 [pmc-release]
AID - 1288362 [pii]
AID - 10.3389/fphar.2024.1288362 [doi]
PST - epublish
SO  - Front Pharmacol. 2024 Jan 24;15:1288362. doi: 10.3389/fphar.2024.1288362. 
      eCollection 2024.