Table 7. Safety subgroup analyses in all trials combined.

	All grade		Severe grade
	RR (95% CI) by BV dosage (mg/kg)		RR (95% CI) by BV dosage (mg/kg)
	2.5 (mg/kg)	5 (mg/kg)	2.5 (mg/kg)	5 (mg/kg)
Hypertension	2.66 (2.15–3.29)	4.71 (3.10–7.15)	4.47 (3.05–6.56)	7.48 (5.04–11.10)
Bleeding	2.35 (1.54–3.60)	3.53 (2.43–5.13)	1.36 (1.05–1.75)	2.87 (1.97–4.18)
Gastrointestinal perforation	2.07 (0.24–18.04)	2.18 (1.12–4.22)	1.86 (0.98–3.55)	2.44 (1.18–5.04)
Proteinuria	2.64 (1.29–5.40)	9.24 (6.60–12.94)	4.18 (2.67–6.55)	6.42 (3.66–11.26)
Epistaxis	2.95 (2.10–4.15)	4.60 (2.35–8.99)	4.85 (0.23–10.56)	3.71 (1.16–11.86)
Stomatitis	1.91 (1.47–2.48)	1.54 (0.69–3.44)	3.62 (0.88–14.84)	3.22 (2.08–4.97)
Rash	1.80 (0.87–3.72)	1.24 (0.48–3.20)	1.80 (0.69–4.59)	2.77 (1.72–4.45)
Neutropenia	1.16 (0.89–1.53)	1.22 (1.04–1.44)	1.03 (0.93–1.14)	1.09 (1.03–1.44)
Febrile neutropenia	1.32 (0.30–5.82)	1.52 (1.01–2.30)	1.37 (1.01–1.85)	1.45 (1.21–1.73)
Fatigue	0.93 (0.78–1.11)	1.05 (0.95–1.17)	0.47 (0.27–0.84)	0.68 (0.33–1.37)
Nausea	1.04 (0.88–1.22)	0.98 (0.87–1.11)	1.19 (0.83–1.71)	1.82 (1.33–2.50)
Vomiting	1.07 (0.88–1.30)	0.84 (0.47–1.50)	1.15 (0.83–1.58)	1.69 (1.04–2.74)
Thrombocytopenia	1.16 (0.88–1.54)	1.40 (0.96–2.02)	0.94 (0.63–1.40)	1.32 (1.00–1.74)
Arterial thromboembolic events	1.91 (0.63–5.79)	1.42 (0.72–2.79)	1.50 (0.98–2.29)	2.78 (1.13–6.85)
Diarrhea	1.04 (0.96–1.14)	1.46 (0.89–2.40)	1.21 (1.03–1.42)	1.23 (0.91–1.67)
Cardiac events *	1.33 (0.19–9.55)	1.19 (0.89–1.61)	0.97 (0.48–1.95)	1.45 (0.93–2.27)
Pulmonary events **	0.72 (0.38–1.38)	0.72 (0.16–3.19)	0.86 (0.36–1.99)	0.74 (0.27–1.99)

Abbreviation: RR: relative risk; BV: bevacizumab.

*Cardiac events including: left ventricular (LV) dysfunction and congestive heart failure.

**Pulmonary events including: embolism, dyspnea, pneumonitis and hemorrhages.