World J Oncol

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 000, Number 000, January 2026, pages 000-000

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

Figure 1. Flow chart of analytical sample screening. AE: adverse event; FDA: US Food and Drug Administration; FAERS: FDA Adverse Event Reporting System.

Figure 2. Strong signals of adverse events associated with TKI medications. (a) Sorafenib. (b) Regorafenib. (c) Lenvatinib. (d) Cabozantinib. TKI: tyrosine kinase inhibitor.

Figure 3. Top 50 strong signals of adverse events associated with four TKI medications. TKI: tyrosine kinase inhibitor.

Figure 4. Comparison of strong signals of adverse events across four TKI medications in overall population. TKI: tyrosine kinase inhibitor.

Figure 5. Comparison of strong signals of adverse events across four TKI medications by gender (a) and age groups (b). AE: adverse event.

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.

**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 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

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	-

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

105

114

110

166

Japan

117

129

China

107

167

Consistent AEs

FDA

Japan

China

Comparison between agencies

FDA vs. EU

FDA vs. Japan

FDA vs. China

EU vs. Japan

EU vs. China

Japan vs. China