Table 1 Main biomarkers and trials of targeted therapies in gastric and esophageal adenocarcinoma

HER2

HER2 amplification/ overexpression

Trastuzumab

ToGA (1st)

Trastuzumab + CX vs CX

OS

Y

[21]

Lapatinib

TRIO-013/LOGiC (1st)

Lapatinib + XELOX vs XELOX

OS

N

[95]

Lapatinib

TyTAN (2nd)

Lapatinib + paclitaxel vs paclitaxel

OS

N

[95]

T-DM1

GATSBY (2nd)

T-DM1 vs taxane

OS

N

[97]

Pertuzumab

JACOB (1st)

Pertuzumab + trastuzumab + CF vs trastuzumab + CF

OS

N

[98]

VEGF-A and VEGFR-2

–

Bevacizumab

AVAGAST (1st)

Bevacizumab + CX vs CX

OS

N

[29]

Ramucirumab

REGARD (2nd)

Ramucirumab vs placebo

OS

Y

[24]

Ramucirumab

RAINBOW (2nd)

Paclitaxel + ramucirumab vs Paclitaxel

OS

Y

[25]

EGFR

EGFR amplification

Cetuximab

EXPAND (1st)

Cetuximab + CX vs CX

PFS

N

[32]

Panitumumab

REAL-3 (1st)

Paniumumab + EOX vs EOX

OS

N

[33]

MET and HGF

MET amplification

Rilotumumab

RILOMET-1 (1st)

Rilotumumab + ECX vs ECX

OS

N

[38]

Onartuzumab

METGastric (1st)

Onartuzumab + FOLFOX vs FOLFOX

OS

N

[39]

FGFR2

FGFR2 polysomy/gene amplification

AZD4547

SHINE (2nd)

AZD4547 vs paclitaxel

PFS

N

[73]

PD-1

–

Nivolumab

ATTRACTION-2 (ONO-4538-12) (≥ 3rd)

Nivolumab vs placebo

OS

Y

[81]

PD-L1 expression

Pembrolizumab

KEYNOTE-059 (≥ 3rd cohort 1; 1st cohort 2 and 3)

Pembrolizumab (cohort 1); Pembrolizumab + CF (cohort 2); Pembrolizumab (cohort 3)

ORR (cohort 1 and 3)

Y

[80]

Pembrolizumab

KEYNOTE-028 (after failure on standard therapy or if standard therapy not appropriate)

Pembrolizumab

ORR

Y

[82]

PD-L1

–

Avelumab

JAVELIN Gastric 300 (3rd)

Avelumab + BSC vs CT

OS

N

[87]