Table 1.
Major Randomized Phase III Trials in the First-Line Setting
| Target-therapy | Year | Pts (N) | Asian (%) | ESCC/GEJC (%) | Regimen | mOS (months) | Results | References | |
|---|---|---|---|---|---|---|---|---|---|
| AVAGAST | 2011 | 774 | 49% | 13% | CF + Bevacizumab vs CF | 12.1 vs 10.1 | Neg | [21] | |
| EXPAND | 2013 | 904 | 38% | 16% | CF + Cetuximab vs CF | 9.4 vs 10.7 | Neg | [22] | |
| REAL-3 | 2013 | 553 | / | 70% | EOC + Panitumumab vs EOC | 8.8 vs 11.3 | Neg | [23] | |
| RILOMET-1 | 2017 | 609 | 1% | 31% | ECF + Rilotumumab vs ECF | 8.8 vs 10.7 | Neg | [24] | |
| MET Gastric | 2017 | 562 | 33% | 23% | FOLFOX + Onartuzumab vs FOLFOX | 11 vs 11.3 | Neg | [25] | |
| RAINFALL | 2019 | 645 | 11% | 25% | CF + Ramucirumab vs CF | 11.2 vs 10.7 | Neg | [26] | |
| HER2-positive | Asian (%) | ESCC/GEJC (%) | Regimen | mOS (months) | Results | ||||
| TOGA | 2010 | 594 | 52% | 18% | CF + Trastu vs CF | 13.8 vs 11.1 | Pos | [13] | |
| HELOISE | 2017 | 248 | 30% | 21% | CF + Trastu maintenance SoC (6 mg/kg) vs HD (10 mg/kg) | 12.5 vs 10.6 | Neg | [27] | |
| LOGIC | 2015 | 545 | 35% | 12% | XELOX + Lapatinib vs XELOX | 12.2 vs 10.5 | Neg | [28] | |
| JACOB | 2018 | 780 | 47% | 27% | Chemo + Trastu + Pertu vs Chemo + Trastu | 17.5 vs 14.2 | Neg | [29] | |
| Immunotherapy | Asian (%) | ESCC (%) | PD-L1 | Regimen | mOS (months) | Results | |||
| KEYNOTE-062 | 2020 | 763 | 24% | 31% | CPS ≥ 1 | Pembro vs CF + Pembro vs CF | 10.6 vs 12.5 vs 11.1 | Neg | [30] |
| ChekMate 649 | 2021 | 1581 | 24% | 30% | CPS ≥5 | Chemo + Nivo vs Chemo | 14.4 vs 11.1 | Pos | [31] |
| Nivo + Ipi vs Chemo | 11.2 vs 11.6 | Neg | |||||||
| ORIENT-16 | 2021 | 650 | 100% | 18% | CPS ≥5 | XELOX + Sintilimab vs XELOX | 18.4 vs 12.9 | Pos | [32] |
| Javelin Gastric 100 | 2021 | 805 | 29% | 23% | / | Maintenance Avelumab vs Chemo | 10.4 vs 10.9 | Neg | [33] |
| Combination Therapy | Asian (%) | ESCC (%) | PD-L1 | Regimen | mOS (months) | Results | |||
| INTEGA | 2022 | 97 | / | 75% | CPS ≥1 | Trastu+ Nivo + FOLFOX vs Trastu+ Nivo + Ipi | 21.8 vs 16.4 | Pos | [34] |
Abbreviations: pts, patients; N, number; ESCC, esophageal squamous cell carcinoma; GEJC, gastroesophageal junction cancer; mOS, median overall survival; CF, cisplatin, 5-fluorouracil; vs, versus; neg, negative; EOC, epirubicin, oxaliplatin, capecitabine; ECF, epirubicin, cisplatin, 5-fluorouracil; FOLFOX, 5-fluorouracil, oxaliplatin; HER2, human epidermal growth factor receptor 2; Trastu, trastuzumab; pos, positive; SoC, standard of care; HD, high dose; XELOX, capecitabine, oxaliplatin; Chemo, chemotherapy; Pertu, pertuzumab; PD-L1, programmed cell death 1; CPS, combined positive score; Pembro, pembrplizumab; Nivo, nivolumab; Ipi, ipilimumab.