Table 1.
Summary of selected targeted agents for advanced gastric cancer
| Target | Study agent | Trial | Treatments | Phase | Biomarker | Results primary end point |
| EGFR | Cetuximab | EXPAND | Arm1: CX + cetuximab | III | No | Negative |
| NCT00678535 | Arm 2: CX | PFS: 4.4 mo vs 5.6 mo (P = 0.32) | ||||
| EGFR | Panitumumab | REAL3 | Arm1: EOC+ Panitumumab | II/III | No | Negative |
| NCT00824785 | Arm2: EOC | OS: 8.8 mo vs 11.3 mo (P = 0.013) | ||||
| mTOR | Everolimus | GRANITE-1 | Arm1: Everolimus | III | No | Negative |
| NCT00879333 | Arm2: Placebo | OS: 5.4 mo vs 4.3 mo (P = 0.124) | ||||
| HER2 | Trastuzumab | ToGA | Arm1: CF + Trastuzumab | III | Yes | Positive |
| NCT01041404 | Arm2: CF | HER2 | OS: 13.8 mo vs 11.1 mo (P = 0.0046) | |||
| HER2/EGFR | Lapatinib | TRIO-013/Logic | Arm1: CX + Lapatinib | III | Yes HER2 | Negative |
| NCT00680901 | Arm2: CX | OS: 12.2 mo vs 10.5 mo (P = 0.35) | ||||
| HER2/EGFR | Lapatinib | TyTAN | Arm1: Paclitaxel + Lapatinib | III | Yes | Negative |
| NCT00486954 | Arm2: Paclitaxel | HER2 | OS: 11.1 mo vs 8.9 mo (P = 0.1044) | |||
| HER2 | Pertuzumab | JACOB | Arm1: CF + Trasuzumab + Pertuzumab | III | Yes | Ongoing |
| NCT0177486 | Arm2: CF + Trastuzumab | HER2 | ||||
| HER2 | T-DM1 | GATSBY | Arm1: Taxane | II/III | Yes | Ongoing |
| NCT01641939 | Arm2: T-DM1 2.4 mg/kg once a week | HER2 | ||||
| Arm3: T-DM1 3.6 mg/kg every 3 wk | ||||||
| VEGF | Bevacizumab | AVAGAST | Arm1: CF + Bevacizumab | III | No | Negative |
| NCT00548548 | Arm2: CF | OS: 12.1 mo vs 10.1 mo (P = 0.1002) | ||||
| VEGFR | Ramucirumab | REGARD | Arm1: Ramucirumab | III | No | Positive |
| NCT00917384 | Arm2: Placebo | OS: 5.2 mo vs 3.8 mo (P = -0.047) | ||||
| VEGFR | Ramucirumab | RAINBOW | Arm1: Paclitaxel + Ramucirumab | III | No | Positive |
| NCT01170663 | Arm2: Paclitaxel | OS: 9.6 mo vs 7.4 mo (P = 0.017) | ||||
| VEGFR | Ramucirumab | RAINFALL | Arm1: CF + Ramucirumab | III | Yes | Ongoing |
| NCT02314117 | Arm2: CF | HER2 negative | ||||
| VEGFR | Apatinib | NCT0152745 | Arm1: Apatinib | III | No | Positive |
| Arm2: Placebo | OS: 6.5 mo vs 4.7 mo (P < 0.016), | |||||
| PFS: 2.6 mo vs 1.8 mo (P < 0.0001) | ||||||
| VEGFR | Regorafenib | INTEGRATE | Arm1: Regorafenib | II | No | Positive |
| (multi-kinase) | Arm2: Placebo | PFS: 11.1 wk vs 3.9 wk (P < 0.0001) | ||||
| VEGFR, PDGFR c-Kit | Pazopanib | PaFLO | Arm1: FLO + Pazopanib | II | Yes | Negative |
| Arm2: FLO | HER2 negative | PFS rate at 6 mo 31.4% vs 25.9% | ||||
| (Did not meet predefined 40%) | ||||||
| MET/HGF | Rilotumumab | RILOMET-1 | Arm1: ECX + Rilotumumab | III | Yes | Terminated due to increased death signal |
| NCT01697072 | Arm2: | MET | Negative (Detrimental) | |||
| OS: 9.6 vs 11.5 mo (HR 1.37, P = 0.016) | ||||||
| MET/HGF | Rilotumumab | RILOMET-2 | Arm1: CX + Rilotumumab | III | Yes | Terminated due to increased death signal |
| NCT02137343 | Arm2: CX | MET | ||||
| MET | Onartuzumab | METGastric | Arm1: FOLFOX | III | Yes | Negative |
| NCT01662869 | Arm2: FOLFOX + Onartuzumab | MET+, HER2- | ITT OS: 11.3 mo vs 11.0 mo (P = 0.24) | |||
| MET2+/3+ OS: 9.7 mo vs 11.0 mo (P = 0.06) | ||||||
| PARP | Olaparib | NCT01063517 | Arm1: Paclitaxel + Olaparib | II | Yes | Negative |
| Arm2: Paclitaxel | ATM | PFS: 3.9 mo vs 2.6 mo (P = 0.261) All patients | ||||
| PFS: 5.3 mo vs 3.7 mo (P = 0.315) ATM- patients | ||||||
| Positive for secondary endpoints | ||||||
| OS: 13.1 mo vs 8.3 mo (P = 0.010) All Patients | ||||||
| OS: NR mo vs 8.2 mo (P = 0.003) ATM- patients | ||||||
| PARP | Olaparib | NCT01924533 | Arm1: Paclitaxel + Olaparib | III | No | Ongoing |
| Arm2: Paclitaxel | ||||||
| Hedgehog | Vismodegib | NCT00982592 | Arm1: FOLFOX + Vismodegib | II | No | Negative |
| Arm2: FOLFOX | PFS: 7.3 mo vs 9.0 mo (P = 0.64) | |||||
| FGFR | Dovitinib | NCT01719549 | Dovitinib monotherapy | II | Yes | Ongoing |
| FGFR | ||||||
| FGFR | Dovitinib | NCT01576380 | Dovitinib monotherapy | II | No | Completed, waiting for result |
| FGFR | Dovitinib | NCT01921673 | Docetaxel + Dovitinib | I/II | No | Ongoing |
| FGFR/VEGFR | AZD4547 | SHINE | Arm1: AZD4547 | II | Yes | Negative |
| NCT1457846 | Arm2: Paclitaxel | FGFR | PFS: 1.8 (AZD) vs 3.5 mo |
EOC: Epirubicin, oxalilatin, capecitabine; CF: Fluoropyrimidine, cisplatin; T-DM1: Trastuzumab emtansine; ECX: Epirubicin, csiplatin, capecitabine; CX: Cisplatin, capecitabine; FOLFOX: 5-Fluorouracil, folinic acid, oxaliplatin; NR: Not reached; FLO: 5-FU, leucovorine, oxaliplatin; EGFR: Epidermal growth factor receptor; mTOR: Mammalian target of rapamycin; HER2: Human epidermal growth factor receptor 2; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor; PDGFR: Platelet-derived growth factor receptor; MET: Mesenchymal-epithelial transition factor; HGF: Hepatocyte growth factor; PARP: Poly ADP-ribose polymerase; FGFR: Fibroblast growth factor receptor.