Table 3.

Incidence and RR of high-grade AEs resulting from regorafenib treatment

AEs	No of studies	No of events/sample size		Incidence (95% CI)		I2 (%)	RR (95% CI)	P-value
		Regorafenib	Placebo/control	Regorafenib	Placebo/control
Any AE	4	610/1,142	83/580	0.54 (0.50–0.57)	0.15 (0.12–0.18)	19	3.73 (3.04–4.59)	<0.00001
Clinical AE
Hand–foot skin reaction	5	192/1,231	2/672	0.16 (0.14–0.18)	0.005 (0.002–0.02)	0	30.28 (10.51–87.22)	<0.00001
Hypertension	6	158/1,328	15/722	0.13 (0.09–0.19)a	0.02 (0.01–0.04)	0	5.85 (3.48–9.84)	<0.00001
Fatigue	4	79/1,142	20/580	0.06 (0.03–0.09)a	0.04 (0.03–0.06)	46	1.97 (1.23–3.16)	0.005
Rash or desquamation	3	38/768	0/387	0.05 (0.04–0.07)	0.005 (0.001–0.02)	0	13.32 (2.62–67.68)	0.002
Diarrhea	5	57/1,231	5/672	0.04 (0.02–0.07)a	0.01 (0.01–0.03)	19	5.55 (2.34–13.17)	<0.0001
Anorexia	6	36/1,328	14/722	0.03 (0.02–0.04)	0.03 (0.02–0.05)	0	1.41 (0.77–2.58)	0.27
Oral mucositis	4	25/1,095	2/604	0.03 (0.02–0.04)	0.006 (0.002–0.02)	6	5.01 (1.54–16.28)	0.007
Myalgia	3	7/357	3/226	0.02 (0.004–0.08)a	0.02 (0.008–0.06)	0	1.66 (0.50–5.45)	0.41
Laboratory abnormalities
Increased AST	3	36/607	10/311	0.06 (0.04–0.08)	0.04 (0.02–0.08)	59	2.95 (0.45–19.40)	0.26
Hypophosphatemia	5	63/1,196	3/656	0.06 (0.04–0.09)a	0.01 (0.002–0.02)	0	9.56 (3.50–26.09)	<0.0001
Hyperbilirubinemia	3	44/1,010	7/514	0.05 (0.02–0.10)a	0.02 (0.007–0.03)	0	3.21 (1.46–7.06)	0.004
Increased ALT	3	25/607	5/311	0.05 (0.02–0.11)a	0.02 (0.005–0.08)a	0	2.38 (0.96–5.89)	0.06
Lipase increase	2	7/225	2/160	0.04 (0.02–0.07)	0.01 (0.003–0.05)	0	2.17 (0.42–11.10)	0.35
Thrombocytopenia	4	27/1,099	1/606	0.03 (0.02–0.04)	0.004 (0.001–0.02)	0	6.28 (1.69–23.29)	0.006

Note:

^aThe incidence and RR of AEs and 95% CI were calculated with a random effects model.

Abbreviations: AE/s, adverse event/s; ALT, alanine aminotransferase; AST, aspartate aminotransferase; RR, relative risk.