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Toihata et al. J Cancer Metastasis Treat 2018;4:24 I http://dx.doi.org/10.20517/2394-4722.2017.82 Page 7 of 10

Table 2. The phase III clinical trials of immunotherapy for esophagogastric junction and gastric adenocarcinoma
Patients Primary
Trial Drug Target Treatment
(EGJ) endpoint
CheckMate 649 Nivolumab PD1 594 Nivolumab and ipilimumab vs. 5-FU and OS
(NCT02872116) CTLA-4 (106) oxaliplatin
KEYNOTE-062 Pembrolizumab PD1 545 Pembrolizumab vs. pembrolizumab, 5-FU and PFS and OS
(NCT02494583) (49) cisplatin
or capecitabine vs. 5-FU and cisplatin
KEYNOTE-061 Pembrolizumab PD1 665 Pembrolizumab vs. paclitaxel PFS and OS
(NCT02370498) (137)
ONO-4538-12 Nivolumab PD1 261 Nivolumab vs. placebo OS
(NCT02267343) (0)

CTLA-4: cytotoxic T-lymphocyte-associated protein 4; OS: overall survival; PD1: programmed death protein 1; 5-FU: 5-fluorouracil; PFS:
progression-free survival

abundance of specific bacterial species in the oral and fecal microbiome enhanced systemic and antitumor
immunity [43,44] . For example, in the patients with advanced tumor who received immunotherapy, the use of
[45]
antibiotics caused poor prognosis. In addition, oral administration of bacteria improved anti-tumor effect .
[46]
Some immune checkpoints, such as lymphocyte activation gene 3 protein (LAG3) , T-cell immunoglobulin
[47]
[48]
and mucin domain 3 (TIM3) , T-cell immune-receptor with Ig and ITIM domains (TIGIT) are being
currently investigated in clinical trials, in order to develop new drugs in the near future.
CONCLUSION
Global standard treatment for metastatic EGJ and gastric adenocarcinoma is the combination of platinum-
agents and fluoropyrimidine. The availability of targeted agents such as trastuzumab or ramucirumab,
have become a new hope to the patients with this aggressive tumor. Immune checkpoint inhibitors have
emerged as a novel therapeutic option. Discovering the best combination of these drugs may lead a dramatic
improvement of the prognosis of these aggressive tumors.

DECLARATIONS
Authors’ contributions
Concept, design, literature search and manuscript preparation: Toihata T
Concept, design, and manuscript editing: Imamura Y
Manuscript review: Watanabe M, Baba H

Financial support and sponsorship
None.

Conflicts of interest
There are no conflicts of interest.

Patient consent
Not applicable.

Ethics approval
Not applicable.

Copyright
© The Author(s) 2018.