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Table 1 Completed phase III trials with targeted agents in advanced gastric cancer

From: Targeted and novel therapy 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

  1. 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