Targeted agents for second-line treatment of advanced hepatocellular carcinoma

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

	Adverse events, n (%)						Treatment-related adverse events, n (%)
	Regorafenib			Placebo			Regorafenib			Placebo
	n = 374			n = 193			n = 374			n = 193
	Any G	G 3	G 4	Any G	G 3	G 4	Any G	G 3	G 4	Any G	G 3	G 4
Any AE	374 (100)	208 (56)	40 (11)	179 (93)	61 (32)	14 (7)	346 (93)	173 (46)	14 (4)	100 (52)	31 (16)	1 (1)
HFSR	198 (53)	47 (13)	NA	15 (8)	1 (1)	NA	196 (52)	47 (13)	NA	13 (7)	1 (1)	NA
Diarrhea	155 (41)	12 (3)	0	29 (15)	0	NA	125 (33)	9 (2)	0	18 (9)	0	0
Fatigue	151 (40)	34 (9)	NA	61 (32)	9 (5)	NA	110 (29)	24 (6)	NA	37 (19)	3 (2)	NA
Hypertension	116 (31)	56 (15)	1 (< 1)	12 (6)	9 (5)	0	87 (23)	48 (13)	1 (< 1)	9 (5)	6 (3)	0
Anorexia	116 (31)	10 (3)	0	28 (15)	4 (2)	0	88 (24)	10 (3)	0	12 (6)	0	0
Increased bilirubin	108 (29)	37 (10)	2 (1)	34 (18)	15 (8)	6 (3)	70 (19)	24 (6)	1 (< 1)	7 (4)	4 (2)	0
Increased AST	92 (25)	37 (10)	4 (1)	38 (20)	19 (10)	3 (2)	48 (13)	16 (4)	3 (1)	15 (8)	9 (5)	1 (1)
Fever	72 (19)	0	0	14 (7)	0	0	14 (4)	0	0	4 (2)	0	0
Nausea	64 (17)	2 (1)	NA	26 (13)	0	NA	40 (11)	1 (< 1)	NA	13 (7)	0	NA
Increased ALT	55 (15)	10 (3)	2 (1)	22 (11)	5 (3)	0	29 (8)	6 (2)	2 (1)	8 (4)	2 (1)	0
Weight loss	51 (14)	7 (2)	NA	9 (5)	0	NA	27 (7)	4 (1)	NA	3 (2)	0	NA
Oral mucositis	47 (13)	4 (1)	0	6 (3)	1 (1)	0	42 (11)	4 (1)	0	5 (3)	1 (1)	0
Vomiting	47 (13)	3 (1)	0	13 (7)	1 (1)	0	27 (7)	1 (< 1)	0	5 (3)	0	0
Cough	40 (11)	1 (< 1)	NA	14 (7)	0	NA	4 (1)	0	NA	2 (1)	0	NA
Hypophosphatemia	37 (10)	30 (8)	2 (1)	4 (2)	3 (2)	0	22 (6)	16 (4)	2 (1)	2 (1)	1(1)	0
Hoarseness	39 (10)	0	NA	1 (1)	0	NA	34 (9)	0	NA	0	0	NA

Adapted from: Bruix et al[14]. G: Grade; AE: Adverse event; HFSR: Hand-foot skin reaction; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; NA: Not applicable.