Targeted agents for second-line treatment of advanced hepatocellular carcinoma

Table 6 Adverse events in the REACH-2 phase III trial occurring in ≥ 10% of patients–Safety population

	Adverse events, n (%)						Treatment-related adverse events, n (%)
	Ramucirumab			Placebo			Ramucirumab			Placebo
	n = 197			n = 95			n = 197			n = 95
	Any G	G 3	G 4	Any G	G 3	G 4	Any G	G 3	G 4	Any G	G3	G 4
Fatigue	54 (27)	7 (4)	NA	16 (17)	3 (3)	NA	28 (14)	2 (1)	NA	5 (5)	0	NA
Peripheral edema	50 (25)	3 (2)	0	13 (14)	0	0	15 (8)	2 (1)	0	5 (5)	0	0
Decreased appetite	46 (23)	3 (2)	0	19 (20)	1 (1)	0	21 (11)	0	NA	4 (4)	0	0
Abdominal pain	39 (20)	3 (2)	NA	12 (13)	2 (2)	NA	8 (4)	1 (1)	1 (< 1)	3 (3)	0	NA
Nausea	37 (19)	0	NA	11 (12)	0	NA	23 (12)	0	0	2 (2)	0	NA
Diarrhea	32 (16)	0	0	13 (14)	1 (1)	0	14 (7)	0	1 (< 1)	5 (5)	1 (1)	0
Headache	28 (14)	0	NA	5 (5)	1 (1)	NA	12 (6)	0	3 (1)	0	0	NA
Constipation	27 (14)	1 (1)	0	19 (20)	1 (1)	0	3 (2)	1 (1)	0	3 (3)	0	0
Insomnia	21 (11)	0	NA	6 (6)	1 (1)	NA	1 (1)	0	NA	0	0	NA
Pyrexia	20 (10)	0	0	3 (3)	0	0	4 (2)	0	2 (1)	1 (1)	0	0
Vomiting	20 (10)	0	0	7 (7)	0	0	5 (3)	0	NA	1 (1)	0	0
Bleeding or hemorrhage events	48 (24)	9 (5)	1 (1)	12 (13)	2 (2)	1 (1)	21 (11)	1 (< 1)	0	5 (5)	0	1 (1)
Epistaxis	27 (14)	1 (1)	0	3 (3)	0	0	14 (7)	0	0	2 (2)	0	0
GI hemorrhage events	12 (6)	7 (4)	0	5 (5)	2 (2)	0	1 (1)	1 (1)	0	0	0	0
Hepatic hemorrhage events	1 (1)	0	1 (1)	0	0	0	0	0	0	0	0	0
Pulmonary hemorrhage events	5 (2)	1 (1)	0	0	0	0	0	0	0	0	0	0
Hypertension	49 (25)	25 (13)	0	12 (13)	5 (5)	0	32 (16)	15 (8)	0	6 (6)	2 (2)	0
Proteinuria	40 (20)	4 (2)	0	4 (4)	0	0	27 (14)	4 (2)	0	3 (3)	0	0
Arterial TE events	5 (3)	0	1 (1)	1 (1)	0	0	4 (2)	0	1 (1)	0	0	0
Venous TE events	2 (1)	0	0	2 (2)	1 (1)	0	1 (1)	0	0	1 (1)	0	0
GI perforation	2 (1)	2 (1)	0	2 (2)	2 (2)	0	1 (1)	1 (1)	0	0	0	0
Congestive heart failure	1 (1)	0	0	1 (1)	1 (1)	0	0	0	0	0	0	0
Fistula	1 (1)	0	0	0	0	0	0	0	0	0	0	0
Liver injury or failure	78 (40)	28 (14)	4 (2)	28 (29)	14 (15)	1 (1)	17 (9)	3 (2)	0	2 (2)	0	0
Ascites	35 (18)	7 (4)	0	7 (7)	2 (2)	0	4 (2)	1 (1)	0	1 (1)	0	0
Hepatic encephalopathy	8 (4)	5 (3)	1 (1)	0	0	0	2 (1)	1 (1)	0	0	0	0
Infusion related reactions	17 (9)	28 (14)	0	3 (3)	0	0	13 (7)	0	0	2 (2)	0	0

Adapted from: Zhu et al[57]. G: Grade; AE: Adverse event; NA: Not applicable; GI: Gastrointestinal; TE: Thromboembolic.