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Copyright ©The Author(s) 2023.
World J Methodol. Jun 20, 2023; 13(3): 79-97
Published online Jun 20, 2023. doi: 10.5662/wjm.v13.i3.79
Table 1 The Cancer Genome Atlas has presented a thorough depiction of the molecular basis of gastric cancer[25]
Subtypes
EBV-positive
MSI
GS
CIN
Frequency, %8.821.719.7449.8
DemographicMale patients (81%)Old age (median 72 yr)Young age (median 59 yr)Not specific
HistologyNot specificNot specificDiffuse Intestinal
Main locationFundus and bodyFundus, body, and antrumMostly diffuse subtypeMajority of tumors at the GEJ
MolecularEBV-CIMP: (1) PD-L1/2, JAK2 overexpression; (2) Mutation in PIK3CA, ARID1A, and BCOR; (3) CDKN2A silencing; (4) Immune cell signaling; and (5) Rare TP53 mutationsGastric-CIMP: (1) Hypermutation in TP53, PIK3CA, ERBB2/3, and ARID1A; (2) MLH1 silencing; (3) Mitotic pathways activation; and (4) Commune changes in the genes of CMH1(1) CDH1 and RHOA mutation; (2) CLDN18-ARHGAP fusion; (3) Cell adhesion; (4) Angiogenesis pathways enriched; and (5) Rare TP53 mutations(1) TP53 mutation; (2) RTK-RAS activation; and (3) Mutations of SMAD4 and APC
alterations
Potential therapeutic points(1) PIK3CA; (2) JAK2; and (3) PD-L1/L2(1) PIK3CA; (2) ERBB2/3; (3) EGFR; (4) PD-L1; and (5) MLH1 silencing(1) RHOA; and (2) CLDN18(1) RTKs; (2) EGFR; (3) VEGFA; (4) CCNE1; (5) CCND1; and (6) CDK6
Table 2 Immunotherapies for advanced gastric cancer patients
Ref.
Drug(s)
Number of patients
Study phase
ORR (%)
Median OS (months)
Median PFS (months)
Results
Muro et al[52]Pembrolizumab391b3311.41.8Pembrolizumab demonstrated a reasonable safety profile and potential antitumor efficacy in metastatic PD-L1-positive GC, warranting further exploration in phase 2 and 3 studies
Fuchs et al[53]Pembrolizumab 259215.55.62.0Pembrolizumab is a potential new therapy option for AGC or AGEJC that has progressed following second-line treatment, demonstrating high and persistent responses. Pembrolizumab has a mechanism of action, duration of response, and toxicity profile that differs from and does not overlap with conventional treatment for gastroesophageal adenocarcinoma
Shitara et al[54]Pembrolizumab vs Paclitaxel3953-9.1/8.3 (Pem/Pac)1.5/4.1 (Pem/Pac)When compared to Paclitaxel, Pembrolizumab did not significantly improve overall survival when administered as a second-line therapy for AGC or AGEJC with PD-L1 CPS of 1 or higher
Bang et al[55]Pembrolizumab vs Pembrolizumab plus chemotherapy 56225.8/60.0 (Pem/Pem+Chem)13.8/20.7 (Pem/Pem+Chem)3.3/6.6 (Pem/Pem+Chem)Pembrolizumab combined chemotherapy showed acceptable tolerability and potential anticancer efficacy in AGC or AGEJC, independent of PD-L1 expression. In patients with PD-L1 CPS ≥ 1, pembrolizumab monotherapy revealed good antitumor efficacy and acceptable safety
Kawazoe et al[56]Pembrolizumab plus chemotherapy542b72.2Not reached9.4For the first-line treatment of AGC or AGEJC patients, chemotherapy with Pembrolizumab shown good effectiveness and a tolerable toxicity profile
Kawazoe et al[57]Pembrolizumab plus Lenvatinib29269.0Not reached7.1In patients with AGC, the combination of Lenvatinib and Pembrolizumab demonstrated promising anti-tumor effectiveness while maintaining a tolerable safety profile
Shitara et al[58]Pembrolizumab vs Pembrolizumab plus chemotherapy vs chemotherapy7633-10.6/11.1 (Pem/chem) CPS ≥ 1; 17.0/10.8 CPS ≥ 10

6.9/6.4 (Pem/chem)

In individuals with untreated AGC or AGEJC, Pembrolizumab was shown to be noninferior to chemotherapy, with less adverse effects. Pembrolizumab alone or in combination with chemotherapy did not outperform treatment in terms of OS and PFS
Kwon et al[60]Pembrolizumab18255.6--A subset of MSI-H GC patients with certain immunological responses at baseline, such as stronger TMB, abundant T cell infiltration, more TCR clonal diversity, and less stem-like exhausted T cells, may not require anything more than anti-PD-1 monotherapy
Yamaguchi et al[63]Pembrolizumab plus SOX vs Pembrolizumab plus SP1002b72.2/80.416.9/17.19.4/8.3In Japanese patients with PD-L1 positive, HER-2 negative AGC or AGEJC, the combination of Pembrolizumab plus SOX or SP as first-line treatment indicated high efficacy and reasonable tolerability
Lee et al[64]Pembrolizumab plus Trastuzumab plus Capecitabine plus Cisplatin 431b/276.719.38.6The use of a quadruplet combination as first-line therapy (Pembrolizumab plus Trastuzumab plus Capecitabine plus Cisplatin) resulted in tumor decrease in HER-2-positive AGC
Satake et al[65]Pembrolizumab vs Pembrolizumab plus chemotherapy vs chemotherapy187322.6/37.7 (Pem/chem); 26.9/31.8 (PD-L1 CPS ≥ 10)22.7/13.8 (Pem/chem); 28.5/14.8 (PD-L1 CPS ≥ 10)4.1/6.5 (Pem/chem); 7.2/6.9 (PD-L1 CPS ≥ 10)Pembrolizumab monotherapy was related with statistically better OS results in patients with AGC or AGEJC with PD-L1 CPS ≥ 1 and CPS ≥ 10 tumors as compared to chemotherapy alone. When compared to chemotherapy, Pembrolizumab monotherapy had a better tolerability profile
Janjigian et al[66]Nivolumab plus Ipilimumab vs Nivolumab1601/224/12 (Niv+Ipi/Niv)6.9/6.2 (Niv+Ipi/Niv)1.6/1.4 (Niv+Ipi/Niv)Nivolumab and Nivolumab in combination with Ipilimumab provide a viable treatment option for individuals with AGEJC
Kang et al[67]Nivolumab vs placebo493311.2/0.05.32/4.141.61/1.45Nivolumab might be a potential therapy option for people with AGC or AGEJC who have been highly pretreated
Boku et al[69]Nivolumab plus SOX vs Nivolumab plus CapeOX77257.1/76.5Not reached9.7/10.6In these individuals, Nivolumab in conjunction with SOX or CapeOX was well tolerated and showed potential efficacy
Nakajima et al[71]Nivolumab plus Paclitaxel plus Ramucirumab431/237.213.15.1As a second-line treatment for AGC, Nivolumab in combination with Paclitaxel and Ramucirumab shown promising antitumor activity with tolerable tolerability
Janjigian et al[72]Nivolumab plus chemotherapy vs chemotherapy1,581351/4114.4/11.17.7/6.1Nivolumab in conjunction with chemotherapy is being considered as a new standard first-line treatment for these individuals
Shah et al[73]Andecaliximab plus Nivolumab vs Nivolumab141210/77.1/5.9-When compared to Nivolumab alone, the combination of Andecaliximab and Nivolumab exhibited a favorable safety profile but did not boost efficacy in these people
Kang et al[74]Nivolumab plus oxaliplatin-based chemotherapy vs placebo plus oxaliplatin-based chemotherapy7242/3-17.45/17.1510.45/8.34In these patients, Nivolumab in conjunction with oxaliplatin-based chemotherapy improved PFS but not OS
Bang et al[76]Avelumab vs chemotherapy37132.2/4.34.6/5.01.4/2.7As compared to chemotherapy, treating these patients in the third-line setting with single-agent Avelumab did not improve OS or PFS. Avelumab, on the other hand, had a more manageable toxicity profile than chemotherapy
Moehler et al[77]Avelumab vs chemotherapy4993-10.4/10.9-In patients with AGC or AGEJC in general, or in a specified PD-L1-positive population, Avelumab maintenance therapy did not give a superior OS when compared to continuing chemotherapy