Table 3. Grade 3 and higher toxicities by meta-analysis for the combined regimen versus chemotherapy or TKI monotherapy.

Subgroup	Trials with data	Risk ratio (95%CI)	P values
Hematologic
Anemia	INTACT 1 [7], INTACT 2 [8], TALENT [9], TRIBUTE [10], FASTACT [13],FASTACT–II [14] and CALGB 30406 [12]	0.98 [0.63, 1.53]	0.93
Leukopenia	INTACT 1 [7], INTACT 2 [8], TALENT [9], TRIBUTE [10] and FASTACT–II [14]	0.97 [0.74, 1.27]	0.84
Thrombocytopenia	INTACT 1 [7], TALENT [9], TRIBUTE [10], CALGB 30406 [12],FASTACT [13] and FASTACT–II [14]	1.15 [0.93, 1.41]	0.20
Neutropenia	INTACT 1 [7], INTACT 2 [8], TALENT [9], TRIBUTE [10], Hirsch [11],CALGB 30406 [12], FASTACT [13] and FASTACT–II [14]	1.23 [0.88, 1.73]	0.23†
Non-hematologic
Rash	INTACT 1 [7], INTACT 2 [8], TALENT [9], TRIBUTE [10], Hirsch [11],CALGB 30406 [12], FASTACT [13] and FASTACT–II [14]	2.08 [0.60, 7.16]	0.25†
Nausea	INTACT 1 [7], INTACT 2 [8], TALENT [9], TRIBUTE [10], Hirsch [11],CALGB 30406 [12], FASTACT [13] and FASTACT–II [14]	0.95 [0.40, 2.23]	0.90†
Vomiting	INTACT 1 [7], INTACT 2 [8], TALENT [9], TRIBUTE [10], Hirsch [11],CALGB 30406 [12], FASTACT [13] and FASTACT–II [14]	1.09 [0.81, 1.48]	0.57
Anorexia	INTACT 1 [7], INTACT 2 [8], TALENT [9], Hirsch [11] and FASTACT [13]	2.01 [1.11, 3.63]	0.02
Fatigue/Asthenia	INTACT 1 [7], INTACT 2 [8], TALENT [9], TRIBUTE [10], Hirsch [11],CALGB 30406 [12], FASTACT [13] and FASTACT–II [14]	1.53 [0.78, 2.99]	0.21†
Diarrhea	INTACT 1 [7], INTACT 2 [8], TALENT [9], TRIBUTE [10], Hirsch [11],CALGB 30406 [12], FASTACT [13] and FASTACT–II [14]	2.70 [1.94, 3.76]	<0.001
Dyspnea	INTACT 2 [8], TALENT [9], TRIBUTE [10], and FASTACT–II [14]	0.88 [0.62, 1.23]	0.45

^†Using random-effects model for heterogeneity.