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safety profile of nivolumab in patients with advanced GC or GEJ cancer was manageable and similar to
that reported in patients with other advanced solid tumors. Based on these results, the Japanese Ministry of
Health, Labor and Welfare approved nivolumab for the treatment of unresectable advanced or recurrent GC
which has progressed after chemotherapy. Currently, trials are ongoing to evaluate the efficacy of immune
checkpoint inhibitors in earlier lines of GC treatment.

Ongoing trials in Japan
The RAINFALL trial is ongoing to evaluate the effectiveness of ramucirumab in combination with Cape/
CDDP compared to Cape/CDDP alone as first-line treatment of metastatic GC or GEJ adenocarcinoma
(NCT02314117). The SOLAR trial, a phase III trial comparing TAS-118 (S-1 plus leucovorin) and oxaliplatin
vs. SP as first-line treatment, is recruiting patients with advanced GC in Japan and Korea (NCT02322593).

Precision medicine for GC
Treatment of cancer is likely to shift and be tailored towards personalized therapy based on detailed molecular
information, known as precision medicine. The Cancer Genome Atlas Research Network reported the results
of molecular classification of GC through integrative genomic analysis, which suggested that GC could be
divided into four subtypes : (1) Epstein-Barr virus-related tumors; (2) microsatellite instability represented
[47]
as elevated mutation rates and MLH1 silencing; (3) genomically stable tumors that are strongly related with
diffuse histology, RHOA mutations, and CLDN18-ARHGAP fusion; and (4) chromosomal instability that
mainly comprises intestinal histology, TP53 mutation, and focal amplification of the receptor tyrosine
kinase. Another study reported that GC can be classified into four subtypes : (1) microsatellite unstable;
[48]
(2) microsatellite stable (MSS) with TP53 mutation; (3) MSS without TP53 mutation; and (4) MSS with
epithelial-to-mesenchymal transition (EMT). This study found that the MSS/EMT subtype was related
to poor prognosis. Further analysis is needed to establish genome-based precision medicine.

CONCLUSION
The main goal of treatment for metastatic GC patients is to prolong patient survival while preserving
quality of life. In addition to the combination of conventional cytotoxic drugs, several newly developed
agents, including targeted molecules and immune checkpoint inhibitors, have shown favorable results in
the treatment of metastatic GC. Efforts should be focused on achieving precision medicine based on the
molecular information of GC.

DECLARATIONS
Authors’ contributions
Concept, design, literature search, and manuscript preparation: Eto K
Manuscript editing: Ida S
Design, manuscript editing, and manuscript review: Watanabe M
Manuscript review: Baba H

Financial support and sponsorship
None.

Conflicts of interest
Authors declare that they have no conflicts of interest.

Patient consent
Not applicable.