Table 1.
Main biomarkers and trials of targeted therapies in gastric and esophageal adenocarcinoma
| Target | Biomarker | Targeted agent | Study (treatment line) | Regimen | Primary endpoint | Positive study Y/N | Refs. |
|---|---|---|---|---|---|---|---|
| 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] |
BSC best supportive care, CF cisplatin + fluoropyrimidine, CT chemotherapy, CX cisplatin + capecitabine, EGFR epidermal growth factor receptor, EOX epirubicin + oxaliplatin + capecitabine, FGFR fibroblast growth factor receptor, FOLFOX 5-fluorouracil + leucovorin + oxaliplatin, HGF hepatocyte growth factor, ORR overall response rate, OS overall survival, PD-1 programmed cell death protein 1, PD-L1 programmed death-ligand 1, PFS progression-free survival, VEGF vascular endothelial growth factor, VEGFR vascular endothelial growth factor receptor, XELOX capecitabine + oxaliplatin