Table 1.

Completed phase III trials with targeted agents in advanced gastric cancer

Targeted pathway	Agent	Trial	Selection biomarker/trial design	Overall survival benefit/months (experimental versus control)
HER2	Trastuzumab	ToGA/1st-line [13]	HER2/chemotherapy with or without trastuzumab	Positive (HR 0.74)/13.8 versus 11.1
	Trastuzumab	HELOISE/1st-line phase IIIb [14]	HER2/chemotherapy with standard-dose versus high-dose trastuzumab	Negative (HR 1.24)/12.5 versus 10.6
	Trastuzumab/pertuzumab	JACOB/1st-line [21]	HER2/trastuzumab plus chemotherapy with pertuzumab or placebo	Negative (HR 0.84)/17.5 versus 14.2
	Trastuzumab emtansine (T-DM1)	GATSBY/2nd-line [29]	HER2/T-DM1 versus taxane	Negative (HR 1.15)/7.9 versus 8.6
	Lapatinib	LoGIC/1st-line [41]	HER2/chemotherapy with lapatinib or placebo	Negative (HR 0.91)/12.2 versus 10.5
	Lapatinib	Tytan/2nd-line [43]	HER2/paclitaxel with or without lapatinib	Negative (HR 0.84)/11.0 versus 8.9
Angiogenesis	Bevacizumab	AVAGAST/1st-line [75]	None/chemotherapy with bevacizumab or placebo	Negative (HR 0.87)/12.1 versus 10.1
	Bevacizumab	AVATAR/1st-line [78]	None/chemotherapy with bevacizumab or placebo in Chinese patients	Negative (HR 1.11)/10.5 versus 11.4
	Ramucirumab	RAINFALL/1st-line [66]	HER2(−)/chemotherapy with ramucirumab or placebo	Negative (HR 0.96)/11.2 versus 10.7
	Ramucirumab	RAINBOW/2nd-line [61]	None/paclitaxel with ramucirumab or placebo	Positive (HR 0.807)/9.6 versus 7.4
	Ramucirumab	REGARD/2nd and 3rd-line [60]	None/ramucirumab versus placebo	Positive (HR 0.776)/5.2 versus 3.8
	Apatinib	NCT01512745/3rd-line [73]	None/apatinib versus placebo	Positive (HR 0.71)/6.5 versus 4.7
PD-1/PD-L1	Nivolumab	ATTRACTION 2/3rd-line [102]	None/nivolumab versus placebo in Asian patients	Positive (HR 0.63)/5.26 versus 4.14
	Pembrolizumab	KEYNOTE-061/2nd-line [96]	PD-L1/pembrolizumab versus paclitaxel	Negative (HR 0.82)/9.1 versus 8.3
	Pembrolizumab	KEYNOTE-181/2nd-line [97]	PD-L1/pembrolizumab versus chemotherapy	Positive (HR 0.69)/9.3 versus 6.7 in PD-L1 ≥ 10%
	Pembrolizumab	KEYNOTE-062/1st-line [98]	PD-L1 & HER2(−)/pembrolizumab alone or pembrolizumab plus chemotherapy versus chemotherapy alone	Noninferior for Pembrolizumab (HR 0.91)/10.6 versus 11.1. Negative for Pembrolizumab and chemotherapy (HR 0.85)/12.5 versus 11.1
	Avelumab	JAVELIN Gastric 300/3rd-line [103]	None/avelumab versus chemotherapy	Negative (HR 1.1)/4.6 versus 5.0
DNA	TAS-102	TAGS/3rd-line [106]	None/TAS-102 versus placebo	Positive (HR 0.69)/5.7 versus 3.6
EGFR	Cetuximab	EXPAND/1st-line [120]	None/chemotherapy with or without cetuximab	Negative (HR 1.03)/9.4 versus 10.7
	Panitumumab	REAL3/1st-line [121]	None/chemotherapy with or without panitumumab	Negative (HR 1.37)/8.8 versus 11.3
STAT3	Napabucasin	BRIGHTER/2nd-line [132]	None/paclitaxel with napabucasin or placebo	Negative (HR 1.01)/6.93 versus 7.36
PARP	Olaparib	GOLD/2nd-line [137]	None/paclitaxel with olaparib or placebo	Negative (HR 0.79 [97.5% CI 0.63–1.00])/8.8 versus 6.9
MMP-9	Andecaliximab	GAMMA-1/1st-line [138]	HER2(−)/mFOLFOX6 with andecaliximab or placebo	Negative (HR 0.93)/12.5 versus 11.8
MET	Onartuzumab	METGastric/1st-line) [144]	MET and HER2(−)/mFOLFOX6 with onartuzumab or placebo	Negative (HR 0.82)/11.0 versus 11.3
	Rilotumumab	RILOMET-1/1st-line) [143]	MET and HER2(−)/chemotherapy with rilotumumab or placebo	Negative (HR 1.34)/8.8 versus 10.7
mTOR	Everolimus	GRANITE-1/3rd-line) [140]	None/everolimus versus placebo	Negative (HR 0.90)/5.4 versus 4.3

HER2 human epidermal growth factor receptor 2, HR hazard ratio, PD-1 programmed death-1, PD-L1 programmed death ligand 1, DNA deoxyribonucleic acid, EGFR epidermal growth factor receptor, STAT3 signal transducer and activator of transcription 3, PARP poly (ADP-ribose) polymerase, MMP-9 matrix metalloproteinase 9, mFOLFOX6 5-fluorouracil/leucovorin/oxaliplatin, MET mesenchymal–epithelial transition, mTOR mammalian target of rapamycin