Table 2. Subgroup analyses of response rates and survival outcomes for the presence of hypertension in bevacizumab-treated patients with metastatic colorectal cancer.

Outcomes	Groups and subgroups	Studies	Sample size	RE	95% CI	P value	I2 (%)
ORR	Bevacizumab dose			RR
	2.5 mg/kg/w	1	119	0.93	0.64 – 1.36	0.716	NA
	5 mg/kg/2w	2	118	3.22	1.95 – 5.30	<0.001	0.0
	5 mg/kg/2w or 7.5 mg/kg/3w	2	175	4.17	1.61 – 10.77	0.003	0.0
	7.5 mg/kg/3w	2	172	1.10	0.62 – 1.94	0.753	37.3
	Hypertension diagnosis
	CTC AE V2.0	2	166	2.13	0.83 – 5.46	0.115	31.8
	CTC AE V3.0	5	389	1.82	0.85 – 3.93	0.126	76.5
	CTC AE V4.0	1	79	3.10	1.82 – 5.26	<0.001	NA
	Hypertension cut-off point in controls
	Grade 0	5	466	1.47	0.82 – 2.64	0.195	69.3
	Grade 1/2	3	168	3.35	2.06 – 5.44	<0.001	0.0
	No. of patients
	< 77	4	208	3.07	0.69 – 13.76	0.142	82.5
	≥ 77	4	426	1.84	0.87 – 3.89	0.110	81.1
PFS	Bevacizumab dose			HR
	2.5 mg/kg/w	1	181	0.61	0.43 – 0.87	0.006	NA
	5 mg/kg/2w	3	178	0.54	0.27 – 1.06	0.075	86.3
	5 mg/kg/2w or 7.5 mg/kg/3w	2	175	0.58	0.41 – 0.82	0.002	0.0
	7.5 mg/kg/3w	2	172	0.68	0.44 – 1.05	0.078	0.0
	Hypertension diagnosis
	CTC AE V2.0	2	166	0.45	0.21– 0.95	0.037	88.1
	CTC AE V3.0	4	304	0.60	0.46 – 0.78	<0.001	0.0
	CTC AE V4.0	3	320	0.66	0.51 – 0.86	0.002	0.0
	Hypertension cut-off point in controls
	Grade 0	5	431	0.62	0.49 – 0.78	<0.001	0.0
	Grade 1/2	4	359	0.55	0.33 – 0.77	0.021	86.2
	No. of patients
	< 79	4	218	0.54	0.30 – 0.95	0.032	79.0
	≥ 79	5	572	0.62	0.51 – 0.76	<0.001	0.0
OS	Bevacizumab dose			HR
	2.5 mg/kg/w	1	181	0.73	0.48 – 1.10	0.128	NA
	5 mg/kg/2w	1	79	0.64	0.38 – 1.08	0.096	NA
	5 mg/kg/2w or 7.5 mg/kg/3w	1	101	0.41	0.26 – 0.66	<0.001	NA
	7.5 mg/kg/3w	2	172	0.47	0.29 – 0.79	0.004	0.0
	Hypertension diagnosis
	CTC AE V2.0	1	127	0.43	0.25 – 0.74	0.002	NA
	CTC AE V3.0	4	280	0.40	0.29 – 0.56	<0.001	0.0
	CTC AE V4.0	2	260	0.69	0.50 – 0.96	0.026	0.0
	Hypertension cut-off point in controls
	Grade 0	4	357	0.41	0.30 – 0.55	<0.001	0.0
	Grade 1/2	3	310	0.66	0.49 – 0.90	0.008	0.0
	No. of patients
	< 84	3	174	0.61	0.39 – 0.94	0.025	0.0
	≥ 84	4	493	0.47	0.32 – 0.67	<0.001	52.4

Abbreviations: ORR: objective response rate; PFS: progression free survival; OS: overall survival; RE: risk estimate; 95% CI: 95% confidence interval; OR: odds ratio; HR: hazard ratio; I²: inconsistency index; CTC: common terminology criteria; AE: adverse events; NA: not available.