Table 2.
Selected pivotal clinical trials in gastric and esophagogastric junction cancers [50].
| Trial | Study Arms | Efficacy Outcomes | Clinical Implications | Ref. | ||
|---|---|---|---|---|---|---|
| ORR | mPFS | mOS | ||||
| HER2 | ||||||
| ToGA n = 594 phase III trial, metastatic HER2+ G/GEJ cancers, first line | CTx (Capecitabine or 5-FU plus Cisplatin) | 35% | 5.5 months | 11.1 months | Trastuzumab plus CTx is standard of care in first-line treatment in metastatic HER2+ disease. | [48] |
| CTx (Capecitabine or 5-FU plus Cisplatin) with Trastuzumab | 47%, p = 0.0017 | 6.7 months, p = 0.0002 | 13.8 months, p = 0.0046 | |||
| DESTINY-Gastric01 n = 188 phase II trial, HER2+ Asian metastatic gastric cancer patients, third or later-line | CTx (Irinotecan or Paclitaxel) | 14% | 3.5 months | 8.4 months | FDA approval for Trastuzumab Deruxtecan in HER2+ G/GEJ cancer patients who have received a prior Trastuzumab-based regimen. No approval in Europe yet. | [51] |
| Trastuzumab Deruxtecan | 51%, p < 0.001 | 5.6 months, p = 0.01 | 12.5 months | |||
| KEYNOTE-811 n = 264 phase III trial, metastatic HER2+ G/GEJ cancers, first-line, interim analysis | CTx (CAPOX or 5FU plus Cisplatin) plus Trastuzumab | 51.9% | No data | No data | No mature data yet. Combination of HER2 targeting and immune checkpoint inhibition might have synergistic effects. | [52] |
| CTx (CAPOX or 5FU plus Cisplatin) plus Trastuzumab with Pembrolizumab | 74.4%, p = 0.00006 | No data | No data | |||
| VEGFR | ||||||
| REGARD n = 355 phase III trial, metastatic G/GEJ cancers, second-line | placebo | 3% | 1.3 months | 3.8 months | Ramucirumab mono therapy is approved for second-line treatment in G/GEJ cancers. | [53] |
| Ramucirumab | 3%, p = 0.76 | 2.1 months, p < 0.0001 | 5.2 months, p = 0.047 | |||
| RAINBOW n = 665 phase III trial, metastatic G/GEJ cancers, second-line | CTx (Paclitaxel) | 16% | 2.9 months | 7.4 months | Ramucirumab in combination with Paclitaxel therapy is approved for second-line treatment in G/GEJ cancers. | [54] |
| CTx (Paclitaxel) with Ramucirumab | 28%, p = 0.0001 | 4.4 months, p = 0.0001 | 9.6 months, p = 0.017 | |||
| PD-1 | ||||||
| ATTRACTION-4 n = 724 phase II trial, metastatic Asian G/GEJ cancer patients, first-line | CTx (S-1 or Capecitabine plus Oxaliplatin) | 47.8% | 8.34 months | 17.15 months | Biomarker-based patient selection is needed. In second-line treatment or later MSI-high G/GEJ cancers do benefit from immune checkpoint blockade. | [55] |
| CTx (S-1 or Capecitabine plus Oxaliplatin) with Nivolumab | 57.5%, p = 0.0088 | 10.45 months, p = 0.0007 | 17.45 months, p = 0.26 | |||
| ATTRACTION-2 n = 493 phase III trial, metastatic Asian G/GEJ cancer patients, third or later-line | placebo | 0% | 1.45 months | 4.14 months | [56] | |
| Nivolumab | 11.2% | 1.61 months, p < 0.0001 | 5.26 months, p < 0.0001 | |||
| CheckMate-649 n = 1581 phase III trial, metastatic patients with oesophageal, gastric or GEJ cancers, first-line | CTx (Capecitabine plus Oxaliplatin or FOLFOX) | 45% | 6.1 months | CPS 5: 11.1 months; All patients: 11.6 months | FDA-approved Nivolumab in combination with chemotherapy as a first-line therapy in metastatic G/EGJ cancers. EMA decision is still pending. | [57] |
| CTx (Capecitabine plus Oxaliplatin or FOLFOX) with Nivolumab | 60%, p < 0.0001 | 7.7 months, p < 0.0001 | CPS 5: 14.4 months, p < 0.0001; All patients: 13.8 months, p = 0.0002 | |||
| Nivolumab plus Ipilimumab | No data | No data | No data | Not pub-yet | ||