Novel therapy for advanced gastric cancer

Table 1 Summary of selected targeted agents for advanced gastric cancer

Target	Study agent	Trial	Treatments	Phase	Biomarker	Results primary end point
EGFR	Cetuximab	EXPAND	Arm1: CX + cetuximab	III	No	Negative
		NCT00678535	Arm 2: CX			PFS: 4.4 mo vs 5.6 mo (P = 0.32)
EGFR	Panitumumab	REAL3	Arm1: EOC+ Panitumumab	II/III	No	Negative
		NCT00824785	Arm2: EOC			OS: 8.8 mo vs 11.3 mo (P = 0.013)
mTOR	Everolimus	GRANITE-1	Arm1: Everolimus	III	No	Negative
		NCT00879333	Arm2: Placebo			OS: 5.4 mo vs 4.3 mo (P = 0.124)
HER2	Trastuzumab	ToGA	Arm1: CF + Trastuzumab	III	Yes	Positive
		NCT01041404	Arm2: CF		HER2	OS: 13.8 mo vs 11.1 mo (P = 0.0046)
HER2/EGFR	Lapatinib	TRIO-013/Logic	Arm1: CX + Lapatinib	III	Yes HER2	Negative
		NCT00680901	Arm2: CX			OS: 12.2 mo vs 10.5 mo (P = 0.35)
HER2/EGFR	Lapatinib	TyTAN	Arm1: Paclitaxel + Lapatinib	III	Yes	Negative
		NCT00486954	Arm2: Paclitaxel		HER2	OS: 11.1 mo vs 8.9 mo (P = 0.1044)
HER2	Pertuzumab	JACOB	Arm1: CF + Trasuzumab + Pertuzumab	III	Yes	Ongoing
		NCT0177486	Arm2: CF + Trastuzumab		HER2
HER2	T-DM1	GATSBY	Arm1: Taxane	II/III	Yes	Ongoing
		NCT01641939	Arm2: T-DM1 2.4 mg/kg once a week		HER2
			Arm3: T-DM1 3.6 mg/kg every 3 wk
VEGF	Bevacizumab	AVAGAST	Arm1: CF + Bevacizumab	III	No	Negative
		NCT00548548	Arm2: CF			OS: 12.1 mo vs 10.1 mo (P = 0.1002)
VEGFR	Ramucirumab	REGARD	Arm1: Ramucirumab	III	No	Positive
		NCT00917384	Arm2: Placebo			OS: 5.2 mo vs 3.8 mo (P = -0.047)
VEGFR	Ramucirumab	RAINBOW	Arm1: Paclitaxel + Ramucirumab	III	No	Positive
		NCT01170663	Arm2: Paclitaxel			OS: 9.6 mo vs 7.4 mo (P = 0.017)
VEGFR	Ramucirumab	RAINFALL	Arm1: CF + Ramucirumab	III	Yes	Ongoing
		NCT02314117	Arm2: CF		HER2 negative
VEGFR	Apatinib	NCT0152745	Arm1: Apatinib	III	No	Positive
			Arm2: Placebo			OS: 6.5 mo vs 4.7 mo (P < 0.016),
						PFS: 2.6 mo vs 1.8 mo (P < 0.0001)
VEGFR	Regorafenib	INTEGRATE	Arm1: Regorafenib	II	No	Positive
(multi-kinase)			Arm2: Placebo			PFS: 11.1 wk vs 3.9 wk (P < 0.0001)
VEGFR, PDGFR c-Kit	Pazopanib	PaFLO	Arm1: FLO + Pazopanib	II	Yes	Negative
			Arm2: FLO		HER2 negative	PFS rate at 6 mo 31.4% vs 25.9%
						(Did not meet predefined 40%)
MET/HGF	Rilotumumab	RILOMET-1	Arm1: ECX + Rilotumumab	III	Yes	Terminated due to increased death signal
		NCT01697072	Arm2:		MET	Negative (Detrimental)
						OS: 9.6 vs 11.5 mo (HR 1.37, P = 0.016)
MET/HGF	Rilotumumab	RILOMET-2	Arm1: CX + Rilotumumab	III	Yes	Terminated due to increased death signal
		NCT02137343	Arm2: CX		MET
MET	Onartuzumab	METGastric	Arm1: FOLFOX	III	Yes	Negative
		NCT01662869	Arm2: FOLFOX + Onartuzumab		MET+, HER2-	ITT OS: 11.3 mo vs 11.0 mo (P = 0.24)
						MET2+/3+ OS: 9.7 mo vs 11.0 mo (P = 0.06)
PARP	Olaparib	NCT01063517	Arm1: Paclitaxel + Olaparib	II	Yes	Negative
			Arm2: Paclitaxel		ATM	PFS: 3.9 mo vs 2.6 mo (P = 0.261) All patients
						PFS: 5.3 mo vs 3.7 mo (P = 0.315) ATM- patients
						Positive for secondary endpoints
						OS: 13.1 mo vs 8.3 mo (P = 0.010) All Patients
						OS: NR mo vs 8.2 mo (P = 0.003) ATM- patients
PARP	Olaparib	NCT01924533	Arm1: Paclitaxel + Olaparib	III	No	Ongoing
			Arm2: Paclitaxel
Hedgehog	Vismodegib	NCT00982592	Arm1: FOLFOX + Vismodegib	II	No	Negative
			Arm2: FOLFOX			PFS: 7.3 mo vs 9.0 mo (P = 0.64)
FGFR	Dovitinib	NCT01719549	Dovitinib monotherapy	II	Yes	Ongoing
					FGFR
FGFR	Dovitinib	NCT01576380	Dovitinib monotherapy	II	No	Completed, waiting for result
FGFR	Dovitinib	NCT01921673	Docetaxel + Dovitinib	I/II	No	Ongoing
FGFR/VEGFR	AZD4547	SHINE	Arm1: AZD4547	II	Yes	Negative
		NCT1457846	Arm2: Paclitaxel		FGFR	PFS: 1.8 (AZD) vs 3.5 mo

EOC: Epirubicin, oxalilatin, capecitabine; CF: Fluoropyrimidine, cisplatin; T-DM1: Trastuzumab emtansine; ECX: Epirubicin, csiplatin, capecitabine; CX: Cisplatin, capecitabine; FOLFOX: 5-Fluorouracil, folinic acid, oxaliplatin; NR: Not reached; FLO: 5-FU, leucovorine, oxaliplatin; EGFR: Epidermal growth factor receptor; mTOR: Mammalian target of rapamycin; HER2: Human epidermal growth factor receptor 2; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor; PDGFR: Platelet-derived growth factor receptor; MET: Mesenchymal-epithelial transition factor; HGF: Hepatocyte growth factor; PARP: Poly ADP-ribose polymerase; FGFR: Fibroblast growth factor receptor.