Treatment options in patients with metastatic gastric cancer: Current status and future perspectives

Table 1 Selected phase III clinical trials of current chemotherapy regimens for patients with advanced gastric cancer in the first-line setting

Ref.	Regimen	No. of patients	Response rate	Median PFS/TTP and OS (mo)
Van Cutsem et al[23]	DCF vs CF	445	37% vs 25%	TTP, 5.6 vs 3.7; OS, 9.2 vs 8.6
Cunningham et al[20]	EOF vs EOX vs ECX vs ECF	1002	42.4% vs 47.9% vs 46.4% vs 40.7%	PFS, 6.5 vs 7.0 vs 6.7 vs 6.2;OS, 9.3 vs 11.2 vs 9.9 vs 9.9
Kang et al[21]	CX vs CF	316	41% vs 29%	PFS, 5.6 vs 5.0; OS, 10.5 vs 9.3
Al-Batran et al[24]	FLC vs FLO	220	34.8% vs 24.5%	PFS, 5.8 vs 3.9; OS, 10.7 vs 8.8
Dank et al[32]	IF vs CF	333	31.8% vs 25.8%	TTP, 5.0 vs 4.2; OS, 9.0 vs 8.7
Koizumi et al[36]	CS vs S	305	54% vs 31%	PFS, 6.0 vs 4.0; OS, 13 vs 11
Ajani et al[39]	CS vs CF	1053	29.1% vs 31.9%	PFS, 4.8 vs 5.5; OS, 8.6 vs 7.9
Yoshida et al[40]	DS vs S	635	38.8% vs 26.8%	PFS, 5.29 vs 4.17; OS, 12.48 vs 10.78

DCF: Docetaxel, cisplatin and fluorouracil; CF: Cisplatin and fluorouracil; EOF: Epirubicin, oxaliplatin and fluorouracil; EOX: Epirubicin, oxaliplatin and capecitabine; ECX: Epirubicin, cisplatin and capecitabine; ECF: Epirubicin, cisplatin and fluorouracil; CX: Cisplatin and capecitabine; FLO: Fluorouracil, leucovorin and oxaliplatin; FLC: Fluorouracil, leucovorin and cisplatin; IF: Irinotecan and cisplatin; CS: Cisplatin and S-1; S: S-1; DS: Docetaxel and S-1; PFS: Progression-free survival; OS: Overall survival; TTP: Time-to progression.

Table 2 Phase-III trials regarding targeted therapies in advanced gastric cancer

Ref.	Study/setting	Treatment	No. of patients	Response rate	Median PFS/TTP and OS (mo)
Anti-HER2 agents
Bang et al[8]	ToGA/first-line	Trastuzumab + CX/CF vs CX/CF	584	47% vs 35%	PFS, 6.7 vs 5.5; OS, 13.8 vs 11.1
Bang et al[47]	TyTAN/second-line	Lapatinib + P vs P	430	NA	PFS, 5.4 vs 4.4; OS, 11.0 vs 8.9
Hecht et al[48]	TRIO-013/LOGiC/first-line	Lapatinib + CAPOX vs CAPOX	545	53% vs 40%	PFS, 6.0 vs 5.4; OS, 12.2 vs 10.5
Anti EGFR1 agents
Lordick et al[55]	EXPAND/first-line	Cetuximab + CX vs CX	904	29% vs 30%	PFS, 4.4 vs 5.6; OS, 9.4 vs 10.7
Waddell et al[56]	REAL-3/first-line	Panitumumab + mEOX vs EOX	553	42% vs 46%	PFS, 6.0 vs 7.4; OS, 8.8 vs 11.3
Anti-VEGF agents
Ohtsu et al[64]	AVAGAST/first-line	Bevacizumab + CX vs placebo + CX	774	46% vs 37.4%	PFS, 6.7 vs 5.3; OS, 12.1 vs 10.1
mTOR inhibitors
Ohtsu et al[76]	GRANITE-1/first-line	Everolimus + BSC vs placebo + BSC	656	4.5% vs 2.1%	PFS, 1.7 vs 1.4; OS, 5.4 vs 4.3

HER2: Human epidermal growth factor receptor 2; EGFR1: Epidermal growth factor receptor 1; VEGF: Vascular endothelial growth factor; mTOR: Mammalian target of rapamycin; CX: Cisplatin and capecitabine; CF: Cisplatin and fluorouracil; P: Paclitaxel; CAPOX: Capecitabine and oxaliplatin; EOX: Epirubicin, oxaliplatin and capecitabine; mEOX: Modified EOX; BSC: Best supportive care; PFS: Progression-free survival; TTP: Time-to progression; OS: Overall survival; NA: Not applicable.

Table 3 Second-line chemotherapy trials in patients with advanced gastric cancer

Ref.	Regimen	No. of patients	Response rate	Median PFS/TTP and OS (mo)
Kang et al[82]	Docetaxel or irinotecan + BSC vs BSC	202	-	TTP, NA; OS, 5.3 vs 3.8
Thuss-Patience et al[83]	Irinotecan vs BSC	40	44% vs 5%	PFS, 2.6 vs NA; OS, 4.0 vs 2.4
Ford et al[84]	Docetaxel + BSC vs BSC	168	7% vs NA	PFS, 5.6 vs 5.0; OS, 5.2 vs 3.6
Shimada et al[85]	Irinotecan + cisplatin vs irinotecan	130	21.9% vs 16.4%	PFS, 4.17 vs 3.03; OS, NA

BSC: Best supportive care; NA: Not applicable; PFS: Progression-free survival; OS: Overall survival; TTP: Time-to progression.