TABLE 3.

Common treatment-related AEs (Grade ≥3) (%).

References	Diarrhea	Hand–foot syndrome	Vomiting	Neutropenia	Leukopenia
irreversible TKIs + chemotherapy vs. reversible TKIs + chemotherapy
Xu et al. (2021)	31.0 vs 8.0	16.0 vs 15.0	6.0 vs 2.0	7.0 vs 5.0	8.0 vs 2.0
Ma et al. (2019)	15.4 vs 4.8	24.6 vs 20.6	4.6 vs 1.6	9.2 vs 3.2	7.7 vs 1.6
Xie et al. (2021)	23.9 vs 8.3	1.1 vs 0	1.1 vs 0.8	7.6 vs 5.3	4.3 vs 7.6
Yang and Wang (2021)	13.8 vs 12.2	3.1 vs 15.6	0 vs 4.4	1.5 vs 3.3	NR
Saura et al. (2020)	24.4 vs 12.5	9.6 vs 11.3	4.0 vs 1.9	NR	NR
Martin et al. (2013)	28.0 vs 10.0	0 vs14.0	4.0 vs 2.0	2.0 vs 4.0	NR
irreversible TKIs + chemotherapy vs other regimens
Yan et al. (2020)	30.8 vs 12.8	15.7 vs 5.3	2.2 vs 1.1	3.8 vs 2.1	3.8 vs 2.1
Tian et al. (2022)	20.0 vs 20.0	10.0 vs 10.0	10.0 vs 10.0	NR	NR
Pellerino et al. (2022)	20.0 vs NR	0 vs NR	10.0 vs.NR	NR	NR
Cunningham et al. (2022)	7.0 vs 11.0	4.4 vs 3.7	8.8 vs2.2	4.0 vs 0	4.0 vs 0
Awada et al. (2016)	30.4 vs 3.8	1.7 vs 3.8	2.5 vs 0.9	13 vs 14.5	8 vs 10.7
Harbeck et al. (2016)	19.0 vs 0	2.0 vs 0	3.0 vs 0	56.0 vs 60.0	19.0 vs 21.0
Cortés et al. (2015)	38.0 vs 10.0	0 vs 0	3.0 vs 0	81.0 vs 21.0	6.0 vs 5.0
irreversible TKIs + chemotherapy(single-arm)
Li et al. (2019)	10.7	3.6	3.6	3.6	3.6
Yin et al. (2022)	16.0	1.3	0.6	9.0	7.1
Yan et al. (2022)	24.0	8.0	2.0	14.0	14.0
Hua et al. (2022b)	14.5	0	1.3	0	NR
Chen et al. (2020)	19.6	6.5	7.7	NR	7.7
Zhang et al. (2021)	4.7	0	0.8	2.4	0
Wang and Huang (2022)	21.5	NR	NR	27.8	29.1
Li et al. (2021)	22.7	NR	1.0	7.2	4.1
Freedman et al. (2019)	29.0	0	4.0	0	0
Wang et al. (2021b)	4.5	0	NR	NR	NR
Saura et al. (2014)	23.0	12.0	0	NR	NR
Chow et al. (2013)	29.0	3.0	2.0	20.0	18.0
Awada et al. (2013)	28.0	NR	39.0	46.0	17.0
Hickish et al. (2022)	8.0	4.0	4.0	38.0	0

Note: TKIs, tyrosine kinase inhibitors; NR, no report.