Checkpoint inhibitors in gastrointestinal cancers: Expectations and reality

Table 1 Summarizes publish and ongoing clinical trials evaluating checkpoint inhibitors in gastrointestinal cancers

Ref.	Phase/n	Agent	Histology distribution	Chemotherapies	ORR	SD	OS
Esophageal cancer
Kojima et al[9], 2016	II/65	Nivolumab	100% squamous	Median prior regimen 3	17.20%	25%	12.1
Doi et al[10], 2015	Ib/23	Pembrolizumab	77% squamous	87% received ≥ 2 prior therapies for metastatic disease	23%	18%	N/A
Gastric cancer
Ralph et al[11], 2010	II/18	Tremelimumab	Adenocarcinoma (gastric and esophageal)	15 received one line, 3 two lines	5%	22%	N/A
Muro et al[13], 2016	Ib/39	Pembrolizumab	Adenocarcinoma of the stomach and the junction	Pretreated	31%	NA	11.4
Le et al[12], 2016	II/59	Nivolumab	Adenocarcinoma of the stomach and the junction	83 % received ≥ 2 prior therapies for metastatic disease	12%	21%	6.8
Chung et al[14], 2016	Ib/62	Avelumab	Adenocarcinoma of the stomach and the junction	Second line treatment	18.2 (PDL1+)	NA	6.3 (PDL1+)
Janjigian et al[15], 2016	I/II/160	Nivolumab	Adenocarcinoma of the stomach and the junction	≥ 2 prior therapies for metastatic disease	14%	NA	5.0
		N(3) + I (1)			10%		4.6
		N(1) + I (3)			25%		6.9
Pancreatic cancer/hepatocellular carcinoma/biliary tract cancers
Royal et al[7], 2010	II/26	Ipilimumab	Pancreatic adenocarcinoma	Pretreated	0%	1/26 after progression	NA
Sangro et al[16], 2013	I/20	Tremelimumab	Advanced hepatocellular carcinoma HCV-induced liver cirrhosis	Pretreated	17.60%	76.40%	NA
El-Khoueiry et al[17], 2015	I/II/41	Nivolumab	Child-Pugh (CP) score ≤ B7 and progressive disease (PD) on, intolerant of, or refusing sorafenib	77% prior sorafenib	23%	NA	72% at 6m
Bang et al[18], 2015	Ib/24	Pembrolizumab	Adenocarcinoma of the gallbladder and biliary tree excluding cancer of the ampulla of vater	≥ 1 chemotherapy and 38% ≥ 3	17%	17%	NA
Colon cancer
Chung et al[19], 2010	Phase II/47	Tremelimumab	Adenocarcinoma of colorectal cancer	Extensive prior chemotherapy	2%	2%	4.8 mo
Topalian et al[20], 2012	I/17	Nivolumab	Advanced colorectal cancer	Heavily pretreated	1/17	0	NA
Brahmer et al[21], 2012	I/18	BMS-936559	Advanced colorectal cancer	Pretreated	0%	NA	NA
Le et al[8], 2015	Phase II	Pembrolizumab	Adenocarcinoma of colorectal carcinoma (MMR proficient versus MMR deficient)	Pretreated	0% vs 40%	NA	2.2 mo vs NR
Anal cancer
Ott et al[22], 2015	Ib/25	Pembrolizumab	Refractory metastatic squamous cell carcinoma of the anal canal	Prior systemic therapies	20%	40%	NA
Morris et al[23], 2016	II/39	Nivolumab	Refractory metastatic squamous cell carcinoma of the anal canal	Previously treated, immunotherapy naïve	21%	58%	NA

ORR: Objective response rate; OS: Overall survival; MMR: Mismatch repair; NR: Not reached; NA: Not available.