Rational Application of First-Line EGFR-TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Table 5

Pooled incidence of grade ≥3 treatment-related adverse events in the two groups.

Events	Study numbers	group, % (95% CI)	TKI group, % (95% CI)	RR (95% CI)	value
Hypertension	6	26.5 (23.1-29.9)	2.8 (1.5-4.1)	4.98 (3.54-6.99)	<0.01
Proteinuria	6	4.8 (3.1-6.4)	0.9 (0-2.6)	13.50 (4.19-43.46)	<0.01
Hemorrhage	4	2.4 (0.9-3.9)	1.5 (0.2-2.8)	1.65 (0.62-4.34)	0.313
Thrombosis	3	1.4 (0.2-2.5)	1.7 (0.4-2.9)	0.79 (0.30-2.11)	0.644
Dermatitis acneiform	3	14.9 (10.6-19.2)	9.6 (6.2-13.1)	1.51 (0.97-2.37)	0.069
Diarrhea	6	3.5 (2.1-5.0)	1.6 (0.4-2.7)	2.58 (1.35-4.91)	0.004
Paronychia	3	2.8 (1.2-4.5)	3.1 (1.4-4.7)	1.02 (0.48-2.17)	0.960
Pruritus	2	1.0 (0-2.1)	0.9 (0-2.1)	1.42 (0.28-7.13)	0.670
Rash	6	2.3 (1.4-3.7)	3.9 (2.4-5.3)-	1.12 (0.81-1.55)	0.494
Stomatitis	3	1.3 (0.3-2.5)	1.3 (0.2-2.3)	1.02 (0.33-3.14)	0.972
Dry skin	3	0.6 (0-1.5)	2.2 (0.3-4.1)	0.65 (0.17-2.46)	0.526
Fatigue	3	1.5 (0.2-2.8)	0.5 (0-1.3)	3.09 (0.75-12.75)	0.119
Decreased appetite	4	2.0 (0.7-3.4)	1.3 (0.3-2.4)	1.53 (0.55-4.25)	0.416
Anemia	4	1.8 (0.6-3.0)	0.6 (0-1.4)	2.33 (0.78-6.95)	0.129
Bilirubin	3	1.4 (0-2.9)	1.0 (0-2.0)	0.78 (0.19-3.11)	0.725
AST	3	4.4 (2.3-6.4)	5.2 (3-7.4)	0.96 (0.558-1.66)	0.893
ALT	3	3.0 (1.3-4.7)	4.1 (2.1-6.1)	0.83 (0.42-1.64)	0.589
Interstitial lung disease	2	0.9 (0-2.1)	0.9 (0-2.1)	0.51 (0.05-5.57)	0.580

ALT: alanine aminotransferase; AST: aspartate aminotransferase; TKI: tyrosine kinase inhibitor; : angiogenic inhibitors combined with TKI.