Table 1.
Recent phase III clinical trials investigating molecular targeting agents in gastric cancer
| Clinical trial | Biomarker | n | Results | Achievement of primary objective | Ref. |
| HER2 inhibitor | |||||
| Capecitabine/cisplatin ± trastuzumab (ToGA) | HER2 | 584 | PFS 6.7 mo vs 5.5 mo, P = 0.0002 | Positive | [8] |
| OS 13.8 mo vs 11.1 mo, P = 0.0046 | |||||
| Capecitabine/oxaliplatin ± lapatinib (LOGiC) | HER3 | 545 | Enrollment done | NP (NCT00680901) | |
| Paclitaxel ± lapatinib (TYTAN) | HER4 | 261 | OS 11.3 mo vs 8.8 mo, P = 0.2088 | Negative | [20] |
| EGFR inhibitor | |||||
| Capecitabine/cisplatin ± cetuximab (EXPAND) | NA | 904 | PFS 5.6 mo vs 4.4 mo, P = 0.3158 | Negative | [21] |
| OS 10.7 mo vs 9.4 mo, P = 0.9547 | |||||
| Increased toxicity | |||||
| Epirubicin/oxaliplatin/capecitabine ± panitumumab (REAL-3) | NA | 553 | PFS 6.0 mo vs 7.4 mo, P = 0.068 | Negative | [22] |
| OS 8.8 mo vs 11.3 mo, P = 0.013 | |||||
| Increased toxicity | |||||
| Angiogenesis inhibitor | |||||
| Capecitabine/cisplatin ± bevacizumab (AVAGAST) | NA | 774 | PFS 6.7 mo vs 5.3 mo, P = 0.0037 | Negative | [23] |
| OS 12.1 mo vs 10.1 mo, P = 0.1002 | |||||
| Ramucirumab vs placebo (REGARD) | NA | 355 | PFS 2.1 mo vs 1.3 mo, P < 0.0001 | Positive | [19] |
| OS 5.2 mo vs 3.8 mo, P = 0.0473 | |||||
| Paclitaxel ± ramucirumab (RAINBOW) | NA | 665 | Enrollment done | NP (NCT01170663) | |
| Afatinib vs placebo | NA | 270 | Enrolling | NP (NCT01512745) | |
| C-MET/HGF pathway inhibitor | |||||
| Epirubicin/cisplatin/capecitabine ± rilotumumab (RILOMET-1) | MET | 450 | Enrolling | NP (NCT01697072) | |
| Fluorouracil/folinic acid/oxaliplatin ± onartuzumab (MetGastric) | MET | 800 | Enrolling | NP (NCT01662869) | |
| HER2 | |||||
| PI3K/Akt/mTOR pathway inhibitor | |||||
| Everolimus vs placebo | NA | 648 | PFS 1.68 mo vs 1.41 mo, P < 0.00001 | Negative | [16] |
| OS 5.39 mo vs 4.34 mo, P = 0.1244 | |||||
| Paclitaxel ± everolimus (AIO-STO-0111) | NA | 480 | Enrolling | NP (NCT01248403) | |
NA: Not applicable; NCT: ClinicalTrials.gov identifier; NP: Not published; OS: Overall survival; PFS: Progression-free survival; PI3K: Phosphatidylinositol 3-kinase; HER: Human epidermal growth factor receptor; mTOR: Mammalian target of rapamycin.