Targeted agents for second-line treatment of advanced hepatocellular carcinoma

Table 4 Adverse events in the CELESTIAL phase III trial occurring in ≥ 10% of patients regardless of causality–Safety population

	Adverse events, n (%)
	Cabozantinib		Placebo
	n = 467		n = 237
	Any G	G 3-41	Any G	G 3-41
Any AE	460 (99)	316 (68)	219 (92)	86 (37)
Diarrhea	251 (54)	46 (10)	44 (19)	4 (2)
Decreased appetite	225 (48)	27 (6)	43 (18)	1 (< 1)
PPE	217 (46)	79 (17)	12 (5)	0
Fatigue	212 (45)	49 (10)	70 (30)	10 (4)
Nausea	147 (31)	10 (2)	42 (18)	4 (2)
Hypertension	137 (29)	74 (16)	14 (6)	4 (2)
Vomiting	121 (26)	2 (< 1)	28 (12)	6 (3)
Increased AST	105 (22)	55 (12)	27 (11)	16 (6)
Asthenia	102 (22)	32 (7)	18 (8)	4 (2)
Dysphonia	90 (19)	3 (1)	5 (2)	0
Constipation	87 (19)	2 (< 1)	45 (19)	0
Abdominal pain	83 (18)	8 (1)	60 (25)	10 (4)
Weight loss	81 (17)	5 (1)	14 (6)	0
Increased ALT	80 (17)	23 (5)	13 (5)	5 (2)
Mucosal inflammation	65 (14)	8 (2)	5 (2)	1 (< 1)
Fever	64 (14)	0	24 (10)	1 (< 1)
Upper abdominal pain	63 (13)	3 (1)	31 (13)	0
Cough	63 (13)	1 (< 1)	26 (11)	0
Peripheral edema	63 (13)	4 (1)	32 (14)	2 (1)
Stomatitis	63 (13)	8 (2)	5 (2)	0
Dyspnea	58 (12)	15 (3)	24 (10)	1 (< 1)
Rash	58 (12)	2 (< 1)	146 (6)	1 (< 1)
Ascites	57 (12)	18 (4)	30 (13)	11 (5)
Dysgeusia	56 (12)	0	5 (2)	0
Hypoalbuminemia	55 (12)	2 (< 1)	12 (5)	0
Headache	52 (11)	1 (< 1)	16 (7)	1 (< 1)
Thrombocytopenia	52 (11)	16 (3)	1 (< 1)	0

¹Mostly grade 3; Adapted from: Abou-Alfa et al[34]. G: Grade; AE: Adverse event; PPE: Palmar-plantar erythrodysesthesia; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.