Molecular classifications of gastric cancers: Novel insights and possible future applications

Table 1 Clinical outcomes of recent trials in gastric and esophagogastric adenocarcinomas

Trial name	Phase of study	Line of treatment	Selected biomarker	Treatment arms	n	Primary endpoint	Outcomes
CIN
TOGA[3]	III	First	HER2 expression/amplification	CF/CX	296	OS	OS: 13.8 mo vs 11.1 mo (HR = 0.74, P = 0.005)
				CF/CX + trastuzumab	298		PFS: 6.7 mo vs 5.5 mo (HR = 0.71, P = 0.0002)
							ORR: 47% vs 35% (P = 0.001)
LOGiC[19]	III	First	HER2 expression/amplification	CapeOX	273	OS	OS: 12.2 mo vs 10.5 mo (HR = 0.91, P = 0.34)
				CapeOx + lapatinib	272		PFS: 6.0 mo vs 5.4 mo (HR = 0.82, P = 0.038)
							ORR: 53% vs 39% (P = 0.003)
TyTAN[20]	III	Second	HER2 amplification by FISH	Paclitaxel	129	OS	OS: 11.0 mo vs 8.9 mo (HR = 0.84, P = 0.104)
				Paclitaxel + lapatinib	132		PFS: 5.4 mo vs 4.4 mo (HR = 0.85, P = 0.244)
							ORR: 27% vs 9% (P < 0.001)
JACOB[21]	III	First	HER2 expression/amplification	Pertuzumab + tFP		OS	Ongoing
				Placebo + tFP
GATSBY[22]	II/III	Second	HER2 expression/amplification	TAX	117	OS	OS: 8.6 mo vs 7.9 mo (HR = 1.15, P = 0.86)
				T-DM1	228		PFS: 2.9 mo vs 2.7 mo (HR = 1.13, P = 0.31)
							ORR: 19.6% vs 20.6%
EXPAND[38]	III	First	Unselected	CX	449	PFS	OS: 10.7 mo vs 9.4 mo (HR = 1.0, P = 0.95)
				CX + cetuximab	445		PFS: 5.6 mo vs 4.4 mo (HR = 1.09, P = 0.32)
REAL-3[39]	III	First	Unselected	EOC	275	OS	OS: 11.3 mo vs 8.8 mo (HR = 1.37, P = 0.013)
				EOC + panitumumab	278		PFS: 7.4 mo vs 6.0 mo (HR = 1.22, P = 0.068)
							ORR: 42% vs 46% (P = 0.42)
RILOMET -1[47]	III	First	MET positive by IHC HER2 negative	ECX	305	OS	OS: 11.5 mo vs 9.6 mo (HR = 1.37, P = 0.016)
				ECX + rilotumumab	304		PFS: 5.7 mo vs 5.7 mo (HR = 1.30, P = 0.016)
							ORR: 39.2% vs 30% (OR = 0.67, P = 0.027)
METGastric[49]	III	First	MET positive by IHC HER2 negative	mFOLFOX	562	OS	OS: 11.3 mo vs 11.0 mo (HR = 0.82, P = 0.244)
				mFOLFOX + ornatuzumab			PFS: 6.8 mo vs 6.7 mo (HR = 0.90, P = 0.429)
							ORR: 41% vs 46% (P = 0.253)
AVAGAST[52]	III	First	Unselected	CX	387	OS	OS: 10.1 mo vs 12.1 mo (HR = 0.87, P = 0.1)
				CX + bevacizumab	387		PFS: 5.3 mo vs 6.7 mo (HR = 0.80, P = 0.037)
							ORR: 37.4% vs 46.0% (P = 0.03)
AVATAR[53]	III	First	Unselected	CX	102	OS	OS: 11.4 mo vs 10.5 mo (HR = 1.11, P = 0.55)
				CX + bevacizumab	100		PFS: 6.0 mo vs 6.3 mo (HR = 0.89, P = 0.47)
							ORR: 34% vs 41% (P = 0.35)
REGARD[54]	III	Progression after TP	Unselected	BSC	117	OS	OS: 3.8 mo vs 5.2 mo (HR = 0.77, P = 0.047)
				BSC + ramucirumab	238		PFS: 1.3 mo vs 2.1 mo (HR = 0.48, P < 0.001)
RAINBOW[55]	III	Second	Unselected	Paclitaxel	335	OS	OS: 7.4 mo vs 9.6 mo (HR = 0.80, P = 0.017)
				Paclitaxel + ramucirumab	330		PFS: 2.9 mo vs 4.4 mo (HR = 0.63, P < 0.0001)
Apatinib[57]	III	Third or more	Unselected	Placebo	91	OS	OS: 4.7 mo vs 6.5 mo (HR = 0.70, P = 0.015)
				Apatinib	176		PFS: 1.8 mo vs 2.6 mo (HR = 0.44, P < 0.001)
							ORR: 0% vs 2.84% (P = 0.16)
MSI
NCT01063517[66]	II	Second	ATM expression	Paclitaxel	62	PFS	OS: 8.3 mo vs 13.1 mo (HR = 0.56, P = 0.01)
				Paclitaxel + olaparib	61		PFS: 3.55 mo vs 3.91 mo (HR = 0.80, P = 0.13)
NCT02589496	II	Second	Unselected	Pembrolizumab		RR	Ongoing
GS
FAST[91]	II	First	CLDN18.2	EOX	161	PFS	OS: 8.7 mo vs 12.5 mo (HR = 0.5)
				EOX + IMAB362			PFS: 5.7 mo vs 7.9 mo (HR = 0.5, P = 0.001)

Most significant target-oriented phase II and phase III trials are presented. In the table are shown in order: name of the trial, phase of the study, line of treatment, biomarker selection, treatment arms, number of enrolled patients, primary endpoint and key outcome results. tPF: Trastuzumab + Platinum + fluorouraci; PF: Platinum + fluoropyrimidine; TAX: Taxane, CF: Cisplatin + fluorouracil; CX: Cisplatin + capecitabine; EOC (or ECX): Epirubicin + oxaliplatin + capecitabine; BSC: Best supportive care; CIN: Chromosomal instability; GS: Genomical stability; MSI: Microsatellite instability.