Copyright ©The Author(s) 2016.
World J Gastroenterol. Aug 14, 2016; 22(30): 6776-6799
Published online Aug 14, 2016. doi: 10.3748/wjg.v22.i30.6776
Table 1 Targeted agents that have been studied for the treatment of gastric neoplasia
Class (target)TypeAgentCurrent status in GC treatmentIndicationsTreatment benefits
HER2 inhibitorsmAbTrastuzumabFDA approval 2010HER2+ metastatic GC↑ OS, ORR, PFS[30]
mAb second generationPertuzumabPhase III clinical trials ongoingHER2+ metastatic/locally advanced unresectable GCUnder investigation[38]
Antibody-drug conjugateTrastuzumab etansinePhase II/III clinical trials ongoingHER2+ advanced GCUnder investigation[39]
TKILapatinibPhase III clinical trialsFirst-line and second-line HER2+ advanced/metastatic GCBenefits in some subgroups of patients; ↑ RR in second-line setting[42,43]
Phase III clinical trials ongoingResectable GCUnder investigation[44]
EGFR inhibitorsmAbCetuximabPhase II/III clinical trialsAdvanced/metastatic GCNo benefits in first-line setting; modest benefit, reduced toxicity in second-line setting[52,57-59]
Humanized mAbPanitumumabPhase III clinical trialsAdvanced GCNo benefits[60]
NimotuzumabPhase II clinical trialsAdvanced GCPromising results in EGFR2+/3+ subgroups of patients[69]
TKIGefitinibPhase I/II/III clinical trials ongoingResectable/advanced and metastatic GCNo benefits[72-74]
ErlotinibPhase IIAdvanced/metastatic GCNo benefits so far; phase II trials pending results[75]
VEGF/VEGFR inhibitorsAnti-VEGF humanized mAbBevacizumabPhase III clinical trialsAdvanced GC, first-line treatment↑ PFS, ORR, benefits in specific subgroups of patients[106-108]
Phase III clinical trialsPerioperative chemotherapy in resectable GCUnder investigation[44,110]
Anti-VEGF humanized mAbRamucirumabFDA approval 2014Advanced GC, second-line treatment↑ OS, PFS[119-122]
TKIApatinibCFDA approval 2014Metastatic GC, third-line treatment↑ OS, PFS[127,129,131]
VEGFR, PDGFR, c-KIT, FMS, FLT inhibitorTKISunitinibPhase I/II clinical trialsAdvanced GC↑ OS, ORR (second-line); promising results[133-136]
RAF, VEGFR, PDGFR inhibitorTKISorafenibPhase I/II clinical trialsAdvanced GC↑ PFS, OS (second-line)[143]; conflicting data[144,145]
VEGFR, PDGFR, c-KIT inhibitorTKIPazopanibPhase I/II clinical trialsAdvanced GCUnder investigation[150-152]
VEGFR, RAF inhibitorTKIRegorafenibPhase I/II ongoing clinical trialsRefractory advanced GC↑ PFS, OS, drawback: drug-related toxicity[156]; under investigation[157-159]
IGF-1 inhibitorHumanized mAbFigitumumabPhase I ongoing clinical trialsAdvanced GCUnder investigation[167,168]
FGF- inhibitorsTKIAZD2171Phase II clinical trialsAdvanced GC, second-line treatmentPromising results[172]
JNJ-42756493Phase I ongoing clinical trialsAdvanced GCPromising results[173]
DovitinibPhase I/II ongoing clinical trialsAdvanced GCUnder investigation[183-185]
HGF/c-MET inhibitorsHumanized mAbRilotumumabPhase II clinical trialsAdvanced/metastatic GC↑ OS in MET (+) subset of patients[188,189]
Phase III clinical trialsIncreased toxicity, ↓ OS, PFS
OnartuzumabPhase III clinical trialsMET(+), HER2(-) GCNegative results
TKIForetonibPhase II clinical trialsMetastatic GCMinimal efficacy[194]
PI3 kinase/mTOR inhibitorsInhibitorEverolimusPhase III clinical trialsAdvanced GC, second/third-line treatmentNegative results[207,208]
SirolimusPhase I ongoing clinical trialsAdvanced GCUnder investigation[209]
PARP inhibitorsInhibitorOlaparibPhase II clinical trialsMetastatic/recurrent GC, second-line treatment↑ OS in specific subgroup of patients; under investigation[211-213]
VeliparibPhase I ongoing clinical trialsAdvanced GCUnder investigation[216]
Immuno-therapy/Immuno-checkpoint blockadeCTLA-4 inhibitorIpilimumabPhase II clinical trialsAdvanced/metastatic GCNegative results[224]
CTLA-4 inhibitorTremalimu-mabPhase I/II ongoing clinical trialsAdvanced GCSynergistic effects for Tremelimumab and Durvalumab combination; under investigation[240,241]
Binding of PD-1 with PD-L1 blockadeNivolumabPhase I/II ongoing clinical trialsAdvanced/metastatic GCPromising results[228]
Pembrolizu-mabPhase I-III ongoing clinical trialsAdvanced/metastatic GC, naive patients and progression under treatmentPromising results[230]; under investigation[231-238,243,244]
PD-L1 inhibitorDurvalumabPhase I clinical trialsAdvanced GCPromising results[239]
GCC inhibitorHumanized mAbMLN0264Phase I/II ongoing clinical trialsAdvanced/metastatic GC, GCC (+)Promising results[247,248]
Tumour cell cycle inhibitorCKIFlavopiridolPhase II clinical trialsAdvanced GCNegative results[251,252]
Tumour cell apoptosisProteasome inhibitorBortezomibPhase II clinical trialsAdvanced/metastatic GCNegative results[262]
MMP inhibitorsInhibitorMarimastatRandomized, double-blind, placebo-controlled studyNon-resectable GC, maintenance treatmentSurvival benefit[265]