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Table 2. Landmark trials of perioperative and palliative chemo/chemoradiotherapy in gastric cancer
Study name (year)/
region Focus of trial Treatment arms Main results (95% CI)
INT-0116 (2001) [41] Adjuvant CRT Surgery alone m-OS: 27 months HR = 1.35 (1.09-1.66)
North America Surgery + 5-FU/LV/RT m-OS: 36 months P = 0.005
ACTS-GC (2007) [44] Adjuvant CT Surgery alone 3-OS: 70.1% HR = 0.68 (0.52-0.87)
Japan Suegery + S-1 3-OS: 80.1% P = 0.003
CLASSIC (2012) [45] Adjuvant CT Surgery alone 3-OS: 59% HR = 0.56 (0.44-0.72)
South Korea Surgery + capecitabine/oxaliplatin 3-OS: 74% P < 0.0001
ARTIST (2012) [46] Adjuvant CRT Surgery (D2 resection) + XP 3-DFS: 74.2% P = 0.086
South Korea Surgery (D2 resection) + XP/RT 3-DFS: 78.2%
ARTIST-II [49] Adjuvant CRT Surgery (D2 resection, node-positive) + XP In progress
South Korea Surgery (D2 resection, node-positive) + XP/RT
MAGIC (2006) [42] Perioperative CT Surgery alone 5-OS: 23% HR = 0.75 (0.60-0.93)
Europe ECF + surgery + ECF 5-OS: 36% P = 0.009
FLOT (2017) [54] Peiroperative CT ECF or ECX + surgery + ECF or ECX m-OS: 35 months HR = 0.77 (0.63-0.94)
Germany FLOT + surgery + FLOT m-OS: 50 months P = 0.012
CRITICS (2011) [47,48] Perioperative CT ECX or EOX + surgery + XP/RT 5-OS: 40.9% P = 0.99
The Netherlands plus adjuvant RT ECX or EOX + surgery + ECX or EOX 5-OS: 41.3%
POET (2009) [55] Neoadjuvant CRT PLF + surgery 3-OS: 27.7% HR = 0.67 (0.41-1.07)
Germany PLF/RT + surgery 3-OS: 47.4% P = 0.07
TOPGEAR (2017) [57] Perioperative CT ECF + surgery + ECF In progress
Australia/New Zealand/ plus neoadujuvant ECF/RT + surgery + ECF Equivalent in gastrointestinal (32% vs. 30%) and
Europe/Canada RT hematological (50% vs. 52%) toxicity
MAGIC-B [59] Perioperative CT ECX + surgery + ECX In progress
UK plus molecular ECX/lapatinib or bevacizumab + surgery +
targeted ECX/lapatinib or bevacizumab

INNOVATION (2016) [58] Perioperative CT FP or XP In progress
Europe plus molecular FP or XP/trastuzumab
targeted
FP or XP/trastuzumab/pertuzumab
V-325 (2006) [65] Palliative CT FP 2-OS: 9% Severe adverse event: 59%
Europe DCF 2-OS: 18% Severe adverse event: 69%
REAL-2 (2008) [51] Palliative CT ECF vs. ECX vs. EOF vs. EOX m-OS: 9.9 vs. 9.9 vs. 9.3 vs. 11.2 months (P = 0.02)
UK 1-OS: 37.7% vs. 40.8% vs. 40.4% vs. 46.8%
ML17032 (2009) [52] Palliative CT XP m-OS: 10.5 months HR = 0.85 (0.64-1.13)
South Korea FP m-OS: 9.3 months P = 0.008
German AIO (2011) [69] Palliative CT BSC m-OS: 2.4 months Symptom improvement: 7%
Germany Irinotecan m-OS: 4.0 months Symptom improvement: 50%
COUGAR-02 (2014) [70] Palliative CT BSC m-OS: 3.6 months HR = 0.67 (0.49-0.92)
UK BSC/docetaxel m-OS: 5.2 months P = 0.01
ToGA (2010) [11] Palliative CT plus XP or FP m-OS: 11.1 months HR = 0.74 (0.60-0.91)
South Korea molecular targeted XP or FP/trastuzumab m-OS: 13.8 months P = 0.005
RAINBOW (2014) [73] Palliative CT plus Paclitaxel m-OS: 7.4 months HR = 0.81 (0.68-0.96)
Germany molecular targeted Paclitaxel/ramucirumab m-OS: 9.6 months P = 0.017
REGARD (2014) [74] Palliative molecular BSC (placebo) m-OS: 3.8 months HR = 0.78 (0.60-1.00)
USA targeted Ramucirumab m-OS: 5.2 months P = 0.047
ATTRACTION (2017) [75] Palliative molecular BSC (placebo) m-OS: 4.1 months HR = 0.63 (0.51-0.78)
South Korea targeted Nivolumab m-OS: 5.3 months P < 0.0001

5-FU: fluorouracil; BSC: best supportive care; CRT: chemoradiotherapy; CT: chemotherapy; DCF: docetaxel/cisplatin/fluorouracil;
DFS: disease free survival; ECF: epirubicin/cisplatin/fluorouracil; ECX: epirubicin/cisplatin/capecitabine; EOF: epirubicin/oxaliplatin/
fluorouracil; EOX: epirubicin/oxaliplatin/capecitabine; FLOT: fluorouracil/leucovorin/oxaliplatin/docetaxel; FP: fluorouracil/cisplatin; HR:
hazard ratio; LV: leucovorin; m-OS: median overall survival; OS: overall survival; PLF: cisplatin/leucovorin/fluorouracil; RT: radiotherapy;
XP: capecitabine/cisplatin

and 52% of patients completed postoperative CT and CRT therapy, to a large extent due to low postoperative
treatment tolerance in Western patients. This study suggested that Western adjunct treatment should shift to