World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://wjon.elmerpub.com

Original Article

Volume 17, Number 2, April 2026, pages 223-236

Strong Signals of Adverse Events in Tyrosine Kinase Inhibitor Therapy for Liver Cancer Treatment

Figures

↓  Figure 1. Flow chart of analytical sample screening. AE: adverse event; FDA: US Food and Drug Administration; FAERS: FDA Adverse Event Reporting System.
Figure 1.
↓  Figure 2. Strong signals of adverse events associated with TKI medications. (a) Sorafenib. (b) Regorafenib. (c) Lenvatinib. (d) Cabozantinib. TKI: tyrosine kinase inhibitor.
Figure 2.
↓  Figure 3. Top 50 strong signals of adverse events associated with four TKI medications. TKI: tyrosine kinase inhibitor.
Figure 3.
↓  Figure 4. Comparison of strong signals of adverse events across four TKI medications in overall population. TKI: tyrosine kinase inhibitor.
Figure 4.
↓  Figure 5. Comparison of strong signals of adverse events across four TKI medications by gender (a) and age groups (b). AE: adverse event.
Figure 5.
↓  Figure 6. (a, b, c) Comparison of strong signals of adverse events across four TKI medications between age under 18, age 18 - 65, and age over 65. TKI: tyrosine kinase inhibitor.
Figure 6.

Tables

↓  Table 1. Demographic Characteristics of Study Events (N = 31, 886)
 
Variables Sample size Overall Sorafenib (n = 6,469) Regorafenib (n = 1,294) Lenvatinib (n = 5,862) Cabozantinib (n = 2,440) Others (n = 17,736)
Age
  Less than 18 133 0.5 (0.4 - 0.6) 0.6 (0.4 - 0.8) 0.1 (0.0 - 0.3) 0.1 (0.0 - 0.2) 0.1 (0.0 - 0.3) 0.7 (0.6 - 0.8)
  18 to 65 10,388 41.3 (40.7 - 41.9) 50.0 (48.6 - 51.3) 51.6 (48.4 - 54.7) 34.8 (33.4 - 36.3) 33.0 (30.6 - 35.4) 40.0 (39.2 - 40.9)
  Greater than 65 14,637 58.2 (57.6 - 58.8) 49.4 (48.0 - 50.8) 48.3 (45.2 - 51.5) 65.1 (63.6 - 66.6) 66.9 (64.5 - 69.3) 59.3 (58.4 - 60.1)
Gender
  Male 23,828 77.9 (77.4 - 78.4) 79.1 (78.1 - 80.1) 77.2 (74.8 - 79.6) 79.6 (78.5 - 80.6) 80.6 (79.0 - 82.2) 76.5 (75.9 - 77.2)
  Female 6,665 21.8 (21.3 - 22.3) 20.6 (19.6 - 21.6) 22.8 (20.4 - 25.2) 20.4 (19.4 - 21.5) 19.4 (17.8 - 21.0) 23.0 (22.3 - 23.7)
  Not specify 93 0.3 (0.2 - 0.4) 0.3 (0.2 - 0.4) - - - 0.5 (0.4 - 0.6)
Outcome
  Critical outcomes 5,976 19.7 (19.2 - 20.1) 20.4 (19.4 - 21.4) 14.0 (12.1 - 15.9) 15.6 (14.7 - 16.6) 21.7 (19.3 - 24.1) 21.1 (20.4 - 21.7)
  Healthcare utilization 11,757 38.7 (38.1 - 39.2) 25.0 (24.0 - 26.1) 24.0 (21.6 - 26.4) 66.9 (65.6 - 68.1) 27.5 (24.9 - 30.1) 35.9 (35.1 - 36.6)
  Chronic condition 203 0.7 (0.6 - 0.8) 0.6 (0.4 - 0.8) 0.9 (0.4 - 1.4) 0.6 (0.4 - 0.8) 1.1 (0.5 - 1.7) 0.7 (0.5 - 0.8)
  Others 12,465 41.0 (40.4 - 41.6) 54.0 (52.7 - 55.2) 61.1 (58.4 - 63.8) 16.9 (15.9 - 17.9) 49.7 (46.8 - 52.7) 42.4 (41.6 - 43.1)
Country of occurrence
  Japan 10,208 34.9 (34.4 - 35.5) 23.5 (22.4 - 24.6) 28.3 (25.8 - 30.8) 68.8 (67.6 - 70.1) 40.1 (38.2 - 42.1) 27.2 (26.5 - 27.9)
  United States 7,825 26.8 (26.3 - 27.3) 26.1 (25.0 - 27.2) 17.7 (15.6 - 19.8) 15.8 (14.8 - 16.8) 37.8 (35.9 - 39.8) 29.9 (29.2 - 30.7)
  Others 11,209 38.3 (37.8 - 38.9) 50.4 (49.1 - 51.6) 54.0 (51.3 - 56.7) 15.4 (14.4 - 16.4) 22.0 (20.4 - 23.7) 42.9 (42.1 - 43.7)
Occupation of reporter
  Medical professionals 26,097 77.7 (77.2 - 78.1) 71.6 (70.5 - 72.7) 77.3 (75.0 - 79.6) 80.9 (79.9 - 81.9) 63.6 (61.7 - 65.5) 80.8 (80.2 - 81.4)
  Non-medical professionals 7,500 22.3 (21.9 - 22.8) 28.4 (27.3 - 29.5) 22.7 (20.4 - 25.0) 19.1 (18.1 - 20.1) 36.4 (34.5 - 38.3) 19.2 (18.6 - 19.8)
Type of cancer
  Hepatocellular carcinoma 27,279 80.7 (80.3 - 81.1) 77.5 (76.5 - 78.5) 83.1 (81.0 - 85.1) 88.1 (87.2 - 88.9) 82.6 (81.1 - 84.1) 79.0 (78.4 - 79.6)
  Hepatic cancer 5,832 17.3 (16.9 - 17.7) 20.1 (19.1 - 21.1) 15.7 (13.7 - 17.7) 11.6 (10.7 - 12.4) 17.2 (15.7 - 18.7) 18.2 (17.6 - 18.8)
  Others 690 2.0 (1.9 - 2.2) 2.4 (2.0 - 2.8) 1.2 (0.6 - 1.8) 0.4 (0.2 - 0.5) 0.2 (0.0 - 0.3) 2.8 (2.5 - 3.0)

 

↓  Table 2. Comparison of Strong Signals From FAERS and ARs Reported by Four Regulatory Agencies
 
Sorafenib Regorafenib Lenvatinib Cabozantinib
AE: adverse event; AR: adverse reactions; FDA: US Food and Drug Administration; FAERS: FDA Adverse Event Reporting System; EU: European Union.
FAERS 373 207 126 110
Drug facts
  FDA 129 43 105 114
  EU 110 65 88 166
  Japan 117 129 87 73
  China 107 61 167 -
Consistent AEs
  FDA 34 8 11 17
  EU 24 9 8 16
  Japan 25 16 7 11
  China 25 8 14 -
Comparison between agencies
  FDA vs. EU 90 35 57 73
  FDA vs. Japan 88 38 48 51
  FDA vs. China 87 33 83 -
  EU vs. Japan 92 58 49 60
  EU vs. China 95 59 82 -
  Japan vs. China 93 53 60 -