Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular carcinoma and non-small cell lung cancer: a meta-analysis

Figures & data

Figure 1 Study flow diagram.

Figure 2 The quality of each trial.

Table 1 Basic information regarding the studies

Study	Year	Tumor type	N	M/F ratio	Region	Participants		Line of apatinib	Outcome index
						Control	Treatment
Li et al^Citation11	2013	Gastric cancer	144	109:33	China	Placebo	Apatinib (850 mg qd or 425 mg bid)	Third line	ORR, DCR, PFS and OS, adverse reaction
Li et al^Citation16	2017	Hepatocellular carcinoma	40	–	China	TACE	Oral apatinib (unknown dose)	Unknown	CR, PR, SD, PD, survival rate of half year/1 year, total survival rate, VEGF and MMP-9 level, adverse reaction
Lu et al^Citation15	2017	Hepatocellular carcinoma	44	33:9	China	TACE	Oral apatinib (500 mg qd) + TACE	Unknown	AFP level, ORR, PFS, adverse reaction
Guo and Jing^Citation14	2017	Nonsquamous non-small-cell lung cancer	39	20:19	China	Received chemotherapy	Oral apatinib (500 mg qd) + docetaxel	Second line	PFS, DCR, ORR, adverse reaction
Wang et al^Citation13	2017	Nonsquamous non-small-cell lung cancer	128	87:41	China	Received chemotherapy	Apatinib + chemotherapy (unknown dose)	Second line	PFS, OS, CR, PR, SD, PD, adverse reaction
Zhang et al^Citation12	2012	Nonsquamous non-small-cell lung cancer	135	–	China	Placebo	Apatinib (750 mg qd)	Third line	CR, PR, SD, PD, PFS, adverse reaction
Li et al^Citation17	2016	Gastric cancer	273	201:66	China	Placebo	Apatinib (850 mg qd)	Third line	CR, PR, SD, PD, OS, PFS, adverse reaction

Abbreviations: ORR, objective response rate; DCR, disease control rate; PFS, progression-free survival; OS, overall survival; CR, complete remission; PR, partial remission; SD, stable disease; PD, progression disease; AFP, alpha fetoprotein.

Table 2 Subgroup analysis of DCR

Subgroup analysis	Total no of studies	Treatment group		Control group		RR (95% CI) of DCR
		Total no of patients	Subjects (SD + PR + CR)	Total no of patients	Subjects (SD + PR + CR)
Tumor type
GC	2	309	114	144	13	4.10 (2.39, 7.02)
HCC	2	40	27	42	20	1.54 (0.66, 3.60)
NSCLC	3	137	85	141	51	1.71 (0.81, 3.60)
Line
Second line	2	47	23	96	40	1.28 (0.60, 2.76)
Third line	3	399	176	189	24	3.39 (2.42, 4.95)
Apatinib dose
850 mg	2	309	114	144	13	4.10 (2.39, 7.02)
750 mg	1	90	62	45	11	2.82 (1.66, 4.80)
500 mg	2	40	29	42	22	1.40 (0.79, 2.46)

Abbreviations: CR, complete remission; PR, partial remission; SD, stable disease; DCR, disease control rate; GC, gastric cancer; HCC, hepatocellular carcinoma; NSCLC, non-small-cell lung cancer.

Figure 3 Meta-analysis of the short-term efficacy and survival benefit of apatinib.

Notes: (A) DCR; (B) ORR; (C) PFS; and (D) OS. Weights are from random-effects analysis.
Abbreviations: DCR, disease control rate; ORR, objective response rate; PFS, progression-free survival; OS, overall survival.

Table 3 Subgroup analysis of PFS

Subgroup analysis	Total no of studies	Total no of patients	HR of apatinib	95% CI
Tumor type
GC	2	414	0.29	0.12, 0.71
HCC	2	44	0.61	0.27, 1.39
NSCLC	3	302	0.4	0.27, 0.58
Line
Second line	2	127	0.48	0.33, 0.70
Third line	3	549	0.3	0.18, 0.50
Apatinib dose
850 mg	2	414	0.29	0.12, 0.71
750 mg	1	135	0.28	0.17, 0.45
500 mg	2	83	0.55	0.32, 0.94

Note: See Figure 3D.

Abbreviations: GC, gastric cancer; HCC, hepatocellular carcinoma; NSCLC, non-small-cell lung cancer.

Table 4 Adverse reactions of the apatinib group vs the control group

Adverse reaction	Study no	RR	Min 95% CI	Max 95% CI	P-value
Myelosuppression	5	1.45	0.52	4.06	0.48
Nausea and vomiting	3	1.00	0.63	1.58	0.99
Hypertension	5	8.38	4.89	14.37	<0.005
Proteinuria	5	2.66	1.72	4.11	<0.005
Hand-foot syndrome	5	11.50	5.68	23.68	<0.005
Diarrhea	4	2.63	1.20	5.79	0.016

Table 5 The sensitivity analyses of the study

Sensitivity analyses	No of studies	RR (95% CI)				HR (95% CI)
		Studies (no of patients)	DCR	Studies (no of patients)	ORR	Studies (no of patients)	PFS	Studies (no of patients)	OS
Total studies	7	7 (n=800)	2.09 (1.21, 3.60)	7 (n=800)	2.18 (1.30, 3.65)	6 (n=760)	0.38 (0.28, 0.52)	3 (n=542)	0.54 (0.35, 0.81)
Liu et al^Citation18 added	8	8 (n=829)	–	8 (n=829)	2.16 (1.39, 3.16)	6 (n=760)	0.38 (0.28, 0.52)	3 (n=542)	0.54 (0.35, 0.82)
Li et al^Citation11 excluded	6	6 (n=656)	1.97 (1.10, 3.94)	6 (n=656)	2.07 (1.23, 3.50)	5 (n=616)	0.43 (0.35, 0.53)	2 (n=398)	0.67 (0.53, 0.85)
Li et al^Citation16 excluded	6	6 (n=760)	2.05 (1.12, 3.74)	6 (n=760)	2.21 (1.22, 3.98)	6 (n=760)	0.38 (0.28, 0.52)	3 (n=542)	0.54 (0.35, 0.81)
Lu et al^Citation15 excluded	6	6 (n=756)	2.35 (1.35, 4.09)	6 (n=756)	3.38 (1.47, 7.77)	5 (n=726)	0.36 (0.25, 0.51)	3 (n=542)	0.54 (0.35, 0.81)
Guo and Jing^Citation14 excluded	6	6 (n=761)	2.12 (1.31, 3.97)	6 (n=761)	2.08 (1.20, 3.61)	5 (n=727)	0.36 (0.25, 0.52)	3 (n=542)	0.54 (0.35, 0.81)
Wang et al^Citation13 excluded	6	6 (n=672)	2.45 (1.31, 4.58)	6 (n=672)	2.22 (1.31, 3.77)	5 (n=632)	0.36 (0.24, 0.53)	2 (n=414)	0.52 (0.27, 0.98)
Zhang et al^Citation12 excluded	6	6 (n=665)	1.99 (1.07, 3.72)	6 (n=665)	2.05 (1.21, 3.47)	5 (n=625)	0.41 (0.29, 0.58)	3 (n=542)	0.54 (0.35, 0.82)
Li et al^Citation17 excluded	6	6 (n=530)	1.79 (1.10, 2.90)	6 (n=530)	2.11 (1.25, 3.56)	5 (n=490)	0.36 (0.24, 0.55)	2 (n=272)	0.49 (0.25, 0.70)

Abbreviations: DCR, disease control rate; ORR, objective response rate; PFS, progression free survival; OS, overall survival.

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