Copyright
©The Author(s) 2024.
World J Gastrointest Oncol. Feb 15, 2024; 16(2): 273-286
Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.273
Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.273
Study | NCT ID | Study phase | Patient population | Sample size | Intervention measures | Finding | Region |
Checkmate 040 | NCT01658878 | I/II | Advanced HCC with or without chronic viral hepatits | 659 | Envafolimab/Pembrolizumab | ORR: 15% vs 20%; DCR: 58% vs 64%; median TTP: 3.4 months vs 4.1 months; median DOR: 17 months vs 9.9 months | Asia, Europe, United States |
Keynote 224 | NCT02702414 | II | Advanced HCC | 156 | Pembrolizumab | ORR: 17%; DCR: 62%; mPFS: 4.9 months; mOS: 12.9% | Asia, Europe, North America |
Reflect | NCT01761266 | Ⅲ | Unresectable HCC | 954 | Lenvatinib/Sorafenib | mOS: 13.6 months vs 12.3 months; mPFS: 7.4 months vs 3.7 months; medianTTP: 8.9 months vs 3.7 months; ORR: 24.1% vs 9.2% | Asia, Europe, North America |
Keynote 524 | NCT03006926 | I | HCC | 104 | Pembrolizumab + Lenvatinib | ORR: 46% vs 36%; DCR: 88% vs 88%; median DOR: 8.6 months vs 12.6 months; mPFS: 9.3 months vs 8.6 months; mOS: 22 months vs 22 months | United States, France, Italy, Japan |
Leap002 | NCT03713593 | III | Advanced HCC | 794 | Pembrolizumab + Lenvatinib/Lenvatinib | mOS: 21.1 months vs 19.0 months; mPFS: 8.2 months vs 8.0 months; ORR: 26.1% vs 17.5%; DCR: 81.3% vs 78.4% | Asia, Europe, United States |
Study117 | NCT03418922 | Ib | HCC | 30 | Lenvatinib + Nivolumab | ORR: 37.5% vs 7.7%; DCR: 62.5% vs 69.2%; 12 mPFS: 30.0% vs 49.2%; 12 mOS: 52.1% vs 51.3% | NA |
COSMIC-312 | NCT03755791 | III | Advanced HCC without prior systemic anticancer therapy | 837 | Cabozantinib + Atezolizumab/Cabozantinib + Sorafenib | mPFS: 6.8 months vs 4.2 months; mOS: 15.4 months vs 15.5 months; ORR: 13% vs 5%; DCR: 82% vs 63% | Asia, Europe, United States |
RESCUE | NCT03463876 | Ⅱ | Advanced HCC | 190 | Camrelizumabfor + Apatinib | ORR: 34.3% vs 23.8%; DCR: 77.1% vs 75.8%; median DOR: 14.8 months vs NE; mPFS: 5.7 months vs 5.5 months | NA |
Imbrave 150 | NCT03434379 | III | locally advanced or metastatic HCC | 558 | Atezolizumab + Bevacizumab/Sorafenib | ORR: 33.2% vs 13.3%; DCR: 72.3% vs 55.1%; median DOR: NE vs 6.3 months | Asia, Europe, United States |
ORIENT-32 | NCT03794440 | II/III | Advanced HCC | 571 | Sintilimab + Bevacizumab/Sorafenib | mOS: NE vs 10.4 months; mPFS: 6.9 months vs 4.3 months; ORR: | China |
Study 22 | NCT02519348 | Ⅱ | Advanced HCC | 332 | Tremelimumab + Durvalumab/Tremelimumab/Durvalumab | mOS: 18.7 months vs 13.6 months vs 15.1 months vs 11.3 months; DCR: 34% vs 39% vs 34% vs 31%; ORR: 24% vs 10.6% vs 7.2% vs 9.5%; median DOR: NR vs 11.17 months vs 23.95 months vs 13.21 months | Asia, United States, Italy |
HIMALAYA | NCT03298451 | III | No prior systemic therapy for unresectable HCC | 1504 | Tremelimumab/Durvalumab | OS: 16.4 months vs 13.8 months; ORR: 20.1% vs 5.1% | Asia, Europe, United States |
Checkmate-9DW | NCT04039607 | III | No prior systemic therapy for Advanced HCC | 732 | Nivolumab + Pembrolizumab/Sorafenib/Lenvatinib | NE | Asia, Europe, United States |
CHANCE001 | NCT04975932 | Retrospective study | HCC | 556 | TACE + PD-L1 inhibitors + Inhibitor molecule targeted drugs/TACE | mPFS: 9.5 months vs 8.0 months; mOS: 19.2 months vs 15.7 months; ORR: 60.1% vs 32.0% | China |
NCT ID | Study phase | Patient population | Intervention measures | Region |
NCT04393220 | II | Advanced HCC | Bevacizumab + Nivolumab | China |
NCT03785210 | II | Primary HCC or liver dominant metastatic cancer from colorectal or pancreatic cancers | Nivolumab + Tadalafil + Vancomycin | United States |
NCT03939975 | II | Advanced HCC | Pembrolizumab/Nivolumab/JS001 | China |
NCT04172506 | I/II | Advanced solid tumors | AK105 | China |
NCT03419897 | II | Previously treated HCC unresectable carcinoma | Atezolizumab | China, Europe |
NCT05471674 | II | Borderline resectable HCC | Nivolumab | China |
NCT03980288 | I | Advanced HCC | CAR-GPC3 T Cell | China |
NCT03841110 | I | Advanced solid tumors | FT500/FT500 + Nivolumab/FT500 + Pembrolizumab/FT500 + Atezolizumab/FT500 + IL-2 + Nivolumab/FT500 + IL-2 + Pembrolizumab/FT500 + IL-2 + Atezolizumab | United States |
NCT04161911 | NA | Advanced HCC | Nivolumab | United States |
NCT03735628 | I | Advanced solid tumors | Copanlisib + Nivolumab | United States, Canada |
NCT04310709 | II | Unresectable or metastatic HCC | Regorafenib/Nivolumab | Korea |
NCT03299946 | I | Locally advanced HCC | Cabozantinib/Nivolumab | United States |
NCT05535998 | Retrospective study | HCC with portal vein tumor thrombus | TACE-HAIC + TKIs + PD-1 inhibitors/TACE | China |
NCT03849469 | I | Advanced solid tumors | Pembrolizumab | United States |
NCT03652077 | I | Advanced solid tumors | INCAGN02390 (TIM3 inhibitors) | United States |
Limitations | Solution |
Most clinical trials do not take into account the etiology of HCC | Subgroup analysis according on real-world causes |
Insufficient exploratory analysis of subgroups during safety evaluation | Further analysis will be performed based on the subject's characteristics (e.g., height, weight, underlying disease) or the subject's population (e.g., sex, age) |
The sample size of some studies was too small and easy to shift the results | Strict adherence to the inclusion and exclusion criteria, increasing the sample size |
Assessing QOL after treatment could help assess the negative impact and clinical decisions of appropriate treatment, but the primary endpoint of most experiments does not include QOL | The primary endpoint, in addition to tumor treatment response and imaging assessment |
Drug target | Drug name | Drug launch time | Listed in China |
PD-1 | Nivolumab | 2017 | No |
PD-1 | Pembrolizumab | 2018 | Yes |
CTLA-4 | Ipilimumab | 2020 | No |
PD-1 | Tislelizumab | 2021 | Yes |
PD-1 | Sintilimab | 2021 | Yes |
PD-1 + CTLA-4 | Tremelimumab + durvalumab | 2022 | No |
- Citation: Pan D, Liu HN, Qu PF, Ma X, Ma LY, Chen XX, Wang YQ, Qin XB, Han ZX. Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy. World J Gastrointest Oncol 2024; 16(2): 273-286
- URL: https://www.wjgnet.com/1948-5204/full/v16/i2/273.htm
- DOI: https://dx.doi.org/10.4251/wjgo.v16.i2.273