Antibiotics and immunotherapy in gastrointestinal tumors: Friend or foe?

Table 2 Completed clinical trials of immune checkpoint inhibitors on gastrointestinal tumors

Trial	Phase	Treatment	ORR% (95%CI)	DCR% (95%CI)	Median PFS months (95%CI)	Median OS months (95%CI)	Adverse events
Esophageal and gastric cancers
	II	Nivolumab (n = 64)	11 (10-28)	27 (31-54)	1.5 (1.4-2.8)	11 (7.3-13)	G3/4 25%; All-grade 73%
ATTRACTION 02	II	Nivolumab (n = 330)	11 (8-16)	40 (34-46)	1.6 (1.5-2.3)	5.3 (4.6-6.4)	G3/4 27%; All-grade 43%
		Placebo (n = 163)	0(0-3.0)	25 (18-34)	1.5 (1.5-1.5)	4.1 (3.4-4.9)	G3/4 4%; All-grade 27%
CHECKMATE32	I/II	Nivolumab 3 (mg/kg)	12 (5-23)	NR	1.4 (1.2-1.5)	6.2 (3.4-12)	G3/4 17%
		Nivolumab 1 + Iplilimumab 3	24 (13-39)	NR	1.4 (1.2-3.8)	6.9 (3.7-12)	G3/4 47%
		Nivolumab 3 + Iplilimumab 1	8.0 (2.0-19)	NR	1.6 (1.4-2.6)	4.8 (3.0-8.4)	G3/4 27%
KEYNOTE59	II	Pembrolizumab (n = 259)	12 (8-16)	27(21.7-32.9)	2.0 (2.0-2.1)	5.5 (4.2-6.5)	G3/4 18%; All-grade 60%
JAVELIN Gastric 300	III	Avelumab (n = 185)	2.2 (0.6-5.4)	22 (16-29)	1.4 (1.5-2.0)	4.6 (3.6-5.7)	G3/4 9.2%
		Chemotherapy (n = 186)	4.3 (1.9-8.3)	44 (37-52)	2.7 (1.8-2.8)	5.0 (4.5-6.3)	G3/4 32%
KEYNOTE61 PDL CPS ≥ 1	III	Pembrolizumab (n = 196)	16 (11-22)	NR	1.5 (1.4-2.0)	9.1 (6.2-11)	G3/4 25%
		Paclitaxel (n = 199)	14 (9.0-19)	NR	4.1 (3.1-4.2)	8.3 (7.6-9.0)	G3/4 35%
Hepatocellular carcinoma
CHECKMATE40	I/II	Nivolumab (dose-escalation)	15 (6.0-28)	58 (43-72)	NR	15 (9.6-20)	G3/4 25%
		Nivolumab (dose-expansion)	20 (15-26)	64	5.4 (3.9-8.5)	NR	G3/4 63%
KEYNOTE224	II	Pembrolizumab (n = 169)	18 (11-26)	62 (52-71)	4.9 (3.4-7.2)	13 (10-16)	G3/4 25%; All-grade 73%
Biliary tract cancer
KEYNOTE28	I	Pembrolizumab (n = 24)	17 (5.0-39)	34	NR	NR	G3/4 17%; All-grade 63%
Pancreatic cancer
	II	Iplilimumab (n = 27)	0	0	NR	NR	NR
	I	Tremelimumab + gemicitabine (n = 34)	NR	NR	NR	7.4 (5.8-9.4)	All-grade 94%
	Ib/II	Pembrolizumab + gemcitabine + nab-paclitaxel (n = 17)	18	76	9.1 (4.9-15.3)	15 (6.8-23)	G3/4 71%; All-grade 100%
Colorectal cancer (dMMR)
	II	Pembrolizumab (n = 10)	40 (12-74)	90 (55-100)	NR	NR	G3/4 41%; All-grade 98%
KHECKMATE 142	II	Nivolumab (n = 74)	31 (21-43)	69 (57-79)	NR	NR	G3/4 20%; All-grade 70%

DCR: Disease control rate; ORR: Objective response rate; OS: Overall survival; PFS: Progression free survival; G: Grade; NR: Not reported; dMMR: Mismatch repair deficiency.