Recent updates of precision therapy for gastric cancer: Towards optimal tailored management

Table 1 Clinical outcomes of recent trials of targeted therapy in advanced gastric and esophagogastric junction adenocarcinoma

Author and trial	Line of treatment	Phase of study	n	Treatment arms	Outcomes
Anti-HGF/cMET antibodies
Cunningham et al[63], RILOMET-1 (2015)	First	III	609	ECX + rilotumumab vs ECX + placebo	OS: 9.6 mo vs 11.5 mo (HR = 1.37, P = 0.016)
					PFS: 5.7 mo vs 5.7 mo (HR = 1.30, P = 0.016)
					ORR: 30% vs 39.2% (OR 0.67, P = 0.027)
Shah et al[65], METGastric (2015)	First	III	562	mFOLFOX + ornatuzumab vs mFOLFOX + placebo	OS: 11.0 mo vs 11.3 mo (HR = 0.82, P = 0.244)
					PFS: 6.7 mo vs 6.8 mo (HR = 0.90, P = 0.429)
					ORR: 46% vs 41% (P = 0.253)
Malka et al[66], PRODIGE 17 ACCORD 20 MEGA (2015)	First	II	162	mFOLFOX alone vs mFOLFOX + panitumumab vs mFOLFOX + rilobumumab	4-mo PFS rate: 71 vs 63 vs 63%
					PFS: 5.8 mo vs 5.2 mo vs 7.6 mo
					ORR: 54% vs 44% vs 50%
Akt/mTOR inhibitors
Hudis et al[68] (2013)	Second/third	I	34	Trastuzumab + Akt inhibitor (MK-2206)	RR (including stable disease): 24%
					Time to progression: 72 d
Ohtsu et al[70] GRANITE (2013)	Second/third	III	646	Everolimus vs BSC	OS: 5.4 mo vs 4.3 mo (HR = 0.90, P = 0.124)
					PFS: 1.7 mo vs 1.4 mo (HR = 0.66, P < 0.001)
					ORR: 4.5% vs 2.1%; DCR: 43.3% vs 22.0%
Shen et al[71] (2014)	First	II	40	Everolimus + cisplatin + HDFL	OS: 10.5 mo (95%CI: 8.6-12.3)
					PFS: 6.9 mo (95%CI: 4.9-8.4)
STAT3 inhibitor
Oh et al[74] (2015)	Second/third	I	25	STAT3 inhibitor (OPB-31121)	RR (including stable disease): 44.4%
Immune checkpoints inhibitors
Ralph et al[89] (2010)	Second	II	18	Tremelimumab	OS: 4.8 mo (95%CI: 4.06-5.59)
					12 mo OS rate: 33% (95%CI: 14-54)
					RR (including stable disease): 27.8%
Bang et al[90], KEYNOTE-012 (2015)	Second/third	I	39	Pembrolizumab (MK-3475)	OS: 11.4 mo; PFS 1.9 mo
					ORR: 22% (95%CI: 10-39)
Yamada et al[93] (2015)	Second/third	I	20	Avelumab (MS0010718C)	PFS: 11.9 wk (95%CI: 6.0-12.3)
					ORR: 15.0% (95%CI: 3.2-37.9)
Multikinase inhibitors
Sun et al[95] (2010)	First	II	44	Sorafenib + docetaxel + cisplatin	OS: 13.6 mo (90%CI: 8.6-16.1)
					PFS: 5.8 mo (90%CI: 5.4-7.4)
					PR: 41% (90%CI: 28-54)
Martin-Richard et al[96], GERCAD (2013)	First	II	40	Sorafenib + oxaliplatin	OS: 6.5 mo (95%CI: 5.2-9.6)
					PFS: 3 mo (95%CI: 2.3-4.1)
					RR (including stable disease): 50.0%
Hecht et al[100], LOGiC (2015)	First	III	487	CapeOx + lapatinib vs CapeOx + placebo	OS: 12.2 mo vs 10.5 mo (HR = 0.91, P = 0.349)
					PFS: 6.0 mo vs 5.4 mo (HR = 0.82, P = 0.0381)
					ORR: 53% vs 39% (P = 0.0031)
Satoh et al[101], TyTAN (2014)	Second	III	261	Lapatinib + paclitaxel vs Paclitaxel alone	OS: 11.0 mo vs 8.9 mo (HR = 0.84, P = 0.1044)
					PFS: 5.4 mo vs 4.4 mo (HR = 0.85, P = 0.2441)
					ORR: 27% vs 9% (P < 0.001)
Pavlakis et al[103], INTEGRATE (2015)	Second/third	II	147	Regorafenib vs placebo	OS: 5.8 mo vs 4.5 mo (HR = 0.74, P = 0.11)
					PFS: 2.6 mo vs 0.9 mo (HR = 0.40, P < 0.0001)
					RR (including stable disease): 44% vs 16%
Lee et al[106] (2015)	First	II	66	CapeOx + pazopanib	PFS: 6.5 mo; OS: 10.5 mo; ORR: 57.6%

ECX: Epirubicin/Cisplatin/Capecitabine; mFOLFOX: 5-fluorouracil/leukovorin/oxaliplatin; OS: Overall survival; HR: Hazard ratio; PFS: Progression free survival; ORR: Objective response rate; BSC: Best supportive care; DCR: Disease control rate; HDFL: High-dose 5-fluorouracil/leucovorin; CapeOx: Capecitabine/oxaliplatin.

Table 2 Ongoing clinical trials of target therapy in advanced gastric and esophagogastric junction adenocarcinoma

Trial identifier	Line of treatment	Phase of study	Treatment arms	Primary endpoint
Akt/mTOR inhibitors
NCT01613950[32]	Second/third	Ib	AUY922/BYL719	MTD
Immune checkpoints inhibitors
NCT02335411 (KEYNOTE-059)[91]	Third	II	Cohort 1: pembrolizumab monotherapy	ORR
			Cohort 2: pembrolizumab + 5-FU/cisplatin or capecitabine/cisplatin
NCT02370498 (KEYNOTE-061)[92]	Second	III	Pembrolizumab vs paclitaxel	PFS, OS
Multikinase inhibitors
NCT02015169[107]	Neoadjuvant	II	XELOX + lapatinib	R0 resection rate
NCT01913639[108]	First	II	FOLFOX + regorafenib	PFS

PFS: Progression free survival; OS: Overall survival; MTD: Maximum tolerated dose; 5-FU: 5-fluorouracin; ORR: Objective response rate; XELOX: Capecitabine/oxaliplatin; FOLFOX: 5-fluorouracil/leucovorin/oxaliplatin; mTOR: Mammalian target of rapamycin.