Efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in treatment of advanced gastric cancer or gastroesophageal junction cancer: A meta-analysis

Table 1 Characteristics of included studies

Ref.	Trial	Clinical trials. gov, No.	Study design	Phase	Case, experimental vs control, (n)	Intervention methods	ORR (%)	DCR (%)	12-mo OS (%)	12-mo PFS (%)
Bang et al[28] 2018	JAVELIN Gastric 300	NCT02625623	RCT	III	371, 185 vs 186	Avelumab 10 mg/kg Q2 W vs paclitaxel 80 mg/m2 or irinotecan 150 mg/m2 1, 8, 15 d of 4-wk cycles.	2.2	22.2	NA	NA
Bang et al[29] 2019	KEYNOTE-059 (cohorts 2 and 3)	NCT02335411	Single-arm	II	31	Pembrolizumab 200 mg on day 1 of 21-d cycles.	25.8	35.5	63.0	NA
Boku et al[30] 2019	ATTRACTION-4	NCT02746796	RCT	II	40, 21 vs 19	Nivolumab 360 mg Q3 W + SOX or Cape OX.	65.8	84.2	NA	NA
Chen et al[31] 2020	ATTRACTION-2	NCT02267343	RCT	III	493, 330 vs 163	Nivolumab 3 mg/kg Q2 W vs placebo 3 mg/kg Q2 W.	11.9	40.3	87.1	9.3
Chung et al[32] 2019	JAVELIN Solid Tumor	NCT01772004	Dose-escalation	I	150	Avelumab 10 mg/kg Q2 W.	6.7	45.3	38.0	12.6
Doi T et al[33] 2019	JAVELIN Solid Tumor JPN trial	NCT01943461	Single-arm	I	40	Avelumab 10 mg/kg Q2 W	10.0	52.5	31.0	NA
Fuchs et al[34] 2018	KEYNOTE-059 (cohorts 1)	NCT02335411	Single-arm	II	259	Pembrolizumab 200 mg Q3 W.	11.6	27.0	23.4	NA
Herbst et al[35] 2019	JVDF	NCT02443324	Single-arm	Ia/b	41	Pembrolizumab 200 mg on day 1 + ramucirumab 10 mg/kg days 1-8.	7.3	51.2	30.8	12.3
Janjigian et al[36] 2018	CheckMate-032	NCT01928394	Dose-escalation	I/II	59	Nivolumab 3 mg/kg Q2 W.	12.0	32.0	39.0	8.0
Kelly et al[37] 2020	NA	NCT02340975	RCT	Ib/II	27	Durvalumab 20 mg/kg + tremelimumab 1 mg/kg Q4W.	7.4	NA	37.0	NA
Muro et al[38] 2016	KEYNOTE-012	NCT01848834	Single-arm	Ib	39	Pembrolizumab 10 mg/ kg Q2 W.	22.0	33.0	42.0	NA
Shah et al[39] 2019	KEYNOTE-180	NCT02559687	Single-arm	II	121	Pembrolizumab 200 mg Q3 W.	9.9	30.6	28.0	NA
Shitara et al[40] 2018	KEYNOTE-061	NCT02370498	RCT	III	592, 296 vs 296	Pembrolizumab 200 mg Q3 W vs paclitaxel 80 mg/m2 1, 8, 15 d of 4-wk cycles	11.1	20.7	40.0	NA

ORR: Objective response rate; DCR: Disease control rate; OS: Overall survival; PFS: Progression-free survival; RCT: Randomized controlled trial; NA: Not available.

Table 2 Meta-analysis of common adverse events with anti-PD-1/PD-L1 antibody therapy

Common AE	Any grade (%)	95%CI	Grade ≥ 3 (%)	95%CI
Fatigue	15.8	11.1-20.5	1.2	0.6-1.9
Infusion reaction	13.8	1.3-26.3	0.6	-0.2-1.4
Pruritus	13.1	9.8-16.4	NA	NA
Decreased appetite	9.6	5.7-13.5	0.9	0.2-1.6
Nausea	9.4	4.1-14.6	1.4	-2.5-5.4
Abdominal pain	9.3	-9.5-28.1	2.8	-3.4-9.0
Diarrhea	8.3	4.7-11.8	0.6	0.2-0.9
Pyrexia	8.0	1.3-14.6	NA	NA
Vomiting	7.8	0.1-15.4	NA	NA
Rash	7.3	5.2-9.4	0.9	-0.1-1.8
Arthralgia	6.2	3.4-9.0	NA	NA
Hypothyroidism	4.4	2.0-6.7	0.4	0-0.9
Elevated AST	4.1	2.1-6.2	1.5	-0.6-3.5
Asthenia	3.2	1.3-5.1	0.7	-0.2-1.6
Elevated ALT	2.7	1.2-4.1	0.9	-0.4-2.1
Pneumonitis	2.7	0-5.4	0.5	0-1.0
Elevated lipase	0.9	-0.4-2.2	0.7	-0.2-1.6
Colitis	0.8	0.2-1.4	0.4	0-0.8

AEs: Adverse events; CI: Confidence interval; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; NA: Not available.

Table 3 P values of Begg and Egger's tests

Test	ORR	DCR	6-mo OS	6-mo PFS	12-mo OS	12-mo PFS	AEs	Grade ≥ 3 AEs
Begg’s P value	0.669	0.945	0.452	0.902	0.161	0.734	0.583	0.760
Egger’s P value	0.973	0.890	0.810	0.448	0.015	0.821	0.924	0.992

ORR: Objective response rate; DCR: Disease control rate; OS: Overall survival; PFS: Progression-free survival; AEs: Adverse events.