Table 1.
Completed clinical trials for the targetable pathways in gastric cancer.
| Pathway | Name | Treatment | Conclusions | Reference |
|---|---|---|---|---|
| Angiogenesis | REGARD | Ramucirumab | OS 5.2 mo vs. 3.8 mo | Fuchs et al. 2014 |
| RAINBOW | Ramucirumab + Pacitaxel | OS 9.6 mo vs. 7.4 mo | Wilke et al. 2014 | |
| Apatinib | Apatinib | PFS 2.6 mo vs 1.8 mo OS 6.5 mo vs. 4.7 mo |
Li et al. 2016 | |
| INTEGRATE | Regorafenib | PFS 2.6 mo vs. 0.9 mo | Pavlakis et al. 2016 | |
| AVAGAST | Bevacizumab + Capecitabine/Cisplatin | PFS 6.7 mo vs. 5.3 mo OS 12.1 vs 10.1 mo |
Ohtsu et al. 2011 | |
| AVATAR | Bevacizumab + Capecitabine/Cisplatin | PFS 6.3 mo vs. 6.0 mo OS 10.5 mo vs 11.6 mo |
Shen et al. 2013 | |
| Ma et al | Bevacizumab + DOF | OS 17.6 mo vs. 16.4 mo DFS 15.2 mo vs. 12.3 TRR 65% vs 42.5% |
Ma et al. 2015 | |
| Moy et al | Regorafenib + mFOLFOX6 | 6 mo PFS 56% | Moy et al. 2020 | |
| HER2 | TRIO-013/LOGiC | Lapatinib + Capecitabine/Oxaliplatin | PFS 6.0 mo vs. 5.4 mo OS 12.2 mo vs. 10.5 mo Response rate 53% vs 39% |
Hecht et al. 2016 |
| Iqbal et al | Lapatinib | OS 4.8 mo Well tolerated with minimal adverse effects |
Iqbal et al. 2011 | |
| TyTAN | Lapatinib + Pacitaxel | OS 11 mo vs. 8.9 mo PFS 5.4 mo vs 4.4 mo |
Satoh et al. 2014 | |
| ToGA | Trastuzumab + Capecitabine/Cisplatin or Fluorouracil/Cisplatin | OS 13.8 mo vs. 11.1 mo | Bang et al. 2010 | |
| T-ACT | Trastuzumab + Pacitaxel | PFS 3.2 mo vs. 3.7 mo OS 10 mo vs. 10 mo ORR 32% vs. 33% |
Makiyama et al. 2020 | |
| GATSBY | Trastuzumab + Pacitaxel/Docetaxel | OS 7.9 mo vs. 8.6 mo | Thuss-Patience et al. 2017 | |
| JACOB | Pertuzumab + Trastuzumab + Capecitabine/Cisplatin or 5-fluorouracil | OS 17.5 mo vs. 14.2 mo | Tabernero et al. 2018 | |
| Shitara et al | Trastuzumab + Chemotherapy | OS 24.7 mo vs. 13.9 mo in HER2+ patients | Shitara et al. 2013 | |
| Shitara et al | Trastuzumab + Irinotectan/Pacitaxel | OS 12.5 mo vs. 8.4 mo | Shitara et al. 2020 | |
| Janjigian et al | Trastuzumab + Pembrolizumab + Capecitabine/Cisplatin or Oxaliplatin | 6 mo PFS 70% Safe combination with minimal adverse effects |
Janjigian et al. 2020 | |
| Bang et al | Margetuximab | Tumor reduction in 78% Well tolerated with only Grade 1/2 toxicities | Bang et al. 2017 | |
| CP-MGAH22-05 | Margetuximab + Pembrolizumab | Well tolerated | Catenacci et al 2020 | |
| RTK | FOLFETUX | Cetuximab + FOLFIRI | ORR 44.1% Well tolerated |
Pinto et al. 2007 |
| Han et al | Cetuximab + FOLFOX6 | 50% response rate OS 9.9 mo |
Han et al. 2009 | |
| Moehler et al | Cetuximab + Irinotecan and 5-fluouracil | ORR 46% Disease control 79% PFS 9 mo OS 16.5 mo |
Moehler et al. 2011 | |
| Kim et al | Cetuximab + Oxaliplatin/Capecitabine | ORR 52.3% PFS 6.5 mo OS 11.8 mo Well tolerated |
Kim et al. 2011 | |
| EXPAND | Cetuximab + Cisplatin/Capecitabine | PFS 4.4 mo vs. 5.6 mo | Lordick et al. 2013 | |
| Rojo et al | Gefitinib | Reduced pEGFR levels in tumors | Rojo et al. 2006 | |
| MMP-9 | Shah et al | Adencalazimab + mFOLFOX6 | ORR 47.5% | Shah et al. 2018 |
| DNA Damage | Bang et al | Olaparib + Paclitaxel | PFS 3.91 mo vs. 3.55 mo OS 13.1 mo vs. 8.3 mo |
Bang et al 2015 |
| GOLD | Olaparib + Paclitaxel | OS 8.8 mo vs. 6.9 mo | Bang et al. 2017 | |
| Friedlander et al | Tislelizumab + Pamiparib | 49 patients achieved objective response | Friedlander et al. 2019 | |
| Immunotherapy | ATTRACTION-2 | Nivolumab | OS 5.26 mo vs. 4.14 mo 12 mo ORR 26.2% vs. 10.9% |
Kang et al. 2017 |
| JAVELIN Gastric 300 | Avelumab + Pacitaxel/Irinotecan | OS 4.6 vs. 5.0 mo PFS 1.4 vs. 2.7 mo ORR 2.2% vs 4.3% |
Bang et al. 2018 | |
| ATTRACTION-4 | Nivolumab + SOX/CapeOX | ORR 57.1% (SOX) 76.5% (CapeOX) PFS 9.7 mo (SOX) 10.6 mo (CapeOX) |
Boku et al. 2019 | |
| KEYNOTE-059 | Pembrolizumab | PD-L1+ ObRR 15.5% Response duration 16.3 mo PD-L1- ObRR 6.4% Response duration 6.9 mo |
Fuchs et al. 2018 | |
| KEYNOTE-061 | Pembrolizumab + Pacitaxel | OS 9.1 vs. 8.3 mo PFS 1.5 mo vs 4.1 mo |
Shitara et al. 2018 | |
| KEYNOTE-062 | Pembrolizumab + Cisplatin/Fluoruracil/Capecitabine | OS 17.4 mo vs. 10.8 mo for CPS>10 for pembro alone OS 12.5 mo vs. 11.1 mo for CPS>10 for pembro + chemo |
Shitara et al. 2020 | |
| KEYNOTE-063 | Pembrolizumab + Pacitaxel | OS 8 mo vs. 8 mo PFS 2 mo vs. 4 mo ObRR 13% vs 19% |
Chung et al. 2022 | |
| JAVELIN Gastric 100 | Avelumab + Chemotherapy | Whole population OS 10.4 mo vs. 10.9 mo PD-L1+ OS 14.9 mo vs 11.6 mo |
Moehler et al. 2021 | |
| CheckMate 649 | Nivolumab + Ipilimumab + Chemotherapy | OS 13.1 mo (Nivo + Chemo) vs. 11.1 mo (Chemo alone) | Janjigian et al. 2021 | |
| KEYNOTE-158 | Pembrolizumab | ObRR 34.3% PFS 4.1 mo OS 23.5 mo |
Marabelle et al. 2020 | |
| Claudin 18.2 | FAST | IMAB362 + EOX | PFS 7.9 mo vs 5.7 mo OS 12.5 mo vs 8.7 mo |
Al-Batran et al. 2016, Sahin et al. 2021 |
OS= Overall Survival, PFS= Progression free survival, ORR= Overall response rate, ObRR= Objective response rate, DFS= Disease free survival, TRR= Total response rate