Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
Abstract
:1. Introduction
2. From Liver Immune System to HCC Immune Disorders
3. Checkpoint Inhibitors
4. Combined Approaches with Checkpoint Inhibitors
5. Conclusions and Future Directions
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Treatments | Mediators | Design | Setting | Primary Outcomes (Finished/Ongoing) | Reference |
---|---|---|---|---|---|
NIVOLUMAB | Anti-PD1 | Dose-escalation Dose-expansion phase trial | Second line in sorafenib pretreated patients | DCR: 55%; ORR: 10%, mOS 9.8 months (finished) | 31 |
NIVOLUMAB vs. SORAFENIB | Anti-PD1 | Phase III trial | First line treatment | mOS (ongoing, preliminary negative results) | 32 |
PEMBROLIZUMAB | Anti-PD1 | Phase II trial | Second line in sorafenib pretreated patients | ORR: 17%; mPFS: 4.9 months; mOS: 12.9 months (finished) | 33 |
PEMBROLIZUMAB vs. PLACEBO | Anti-PD1 | Phase III trial | Second line | Improved OS (HR: 0.78; p = 0.0238) and PFS (HR: 0.78; p = 0.0209)—does not meet significance per the prespecified statistical plan (ongoing, preliminary negative results) | 34 |
TORIPALIMAB | Anti-PD1 | Phase II trial | Adiuvant setting | Recurrence-freesurvival (ongoing) | 41 |
TREMELIMUMAB | Anti-CTLA4 | Phase II trial | Pretreated advanced HCC from hepatitis C viral etiology | 18% of PR and a 60% of SD (finished) | 35 |
NIVOLUMAB plus IPILIMUMAB | Anti-CLA4 plus Anti-PD1 | Phase I-II trial | Neoadjuvant treatment | Delay to surgery Incidence of treatment-emergent adverse events (ongoing) | 38 |
NIVOLUMAB plus IPILIMUMAB | Anti-CLA4 plus Anti-PD1 | Phase II trial | Neoadjuvant treatment | The percentage of subjects with tumor shrinkage after drug treatment study (ongoing) | 39 |
ATEZOLIZUMAB plus BEVACIZUMAB | Anti-PD1 plus antiangiogenic drug | Phase II trial | First line treatment | 61% PR with a relatively positive tolerability (finished) | 45 |
ATEZOLIZUMAB plus BEVACIZUMAB vs. SORAFENIB | Anti-PD1 plus antiangiogenic drug | Phase III trial | Metastatic and/or unresectable HCC (first line) | OS/PFS (ongoing) | 46 |
DURVALUMAB (D) plus BEVACIZUMAB (B) vs. D vs. placebo | Anti-PDL1 plus antiangiogenic drug | Phase III trial | Adjuvant setting | Recurrence-free survival (ongoing) | 47 |
LENVATINIB plus PEMBROLIZUMAB | Anti-PD1 plus TKI | Phase 1b trial | unresectable HCC (first line) | 46% of PR and 46% of SD (finished) | 48 |
LENVATINIB (L) plus PEMBROLIZUMAB vs. L | Anti-PD1 plus TKI | Phase III trial | Advanced HCC (first line) | PFS/OS (ongoing) | 49 |
NIVOLUMAB (N) vs. IPILIMUMAB (I) + N vs. SORAFENIB N vs. CABOZANTINIB (C) + N vs. SORAFENIB (CP−A) vs. N+C+I | Anti-PD1 and Anti-CTLA4 plus TKI | Phase I-II trial | CP-A HCC CP-B HCC | Safety and Tolerability (ongoing) | 50 |
TACE, radiofrequency ablation, or cryoablation plus TREMELIMUMAB | Anti-CTLA4 plus interventional radiological procedures | Phase 1b trial | Locally advanced HCC | 23.5% of PR (finished) | 56 |
PEMBROLIZUMAB plus TACE | Anti-PD1 plus interventional radiological procedures | Phase I-II trial | Locally advanced HCC | Safety and Tolerability (ongoing) | 52 |
NIVOLUMAB plus TACE | Anti-PD1 plus interventional radiological procedures | Early phase I trial | Locally advanced HCC | Safety and Tolerability (ongoing) | 53 |
PEMBROLIZUMAB plus yttrium90 radioembolization | Anti-PD1 plus interventional radiological procedures | Early phase I trial | Locally advanced HCC | PFS (ongoing) | 54 |
NIVOLUMAB plus yttrium90 radioembolization | Anti-PD1 plus interventional radiological procedures | Early phase I trial | Locally advanced HCC | Recurrence rate (ongoing) | 55 |
SHR-1210 + ApatinibSHR-1210 + FOLFOX4 or GEMOX regimen | Anti-PD1 plus chemotherapy or TKI | Phase II trial | Advanced Primary Liver Cancer | Safety and Tolerability (ongoing) | 57 |
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Longo, V.; Brunetti, O.; Gnoni, A.; Licchetta, A.; Delcuratolo, S.; Memeo, R.; Solimando, A.G.; Argentiero, A. Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma. Medicina 2019, 55, 698. https://doi.org/10.3390/medicina55100698
Longo V, Brunetti O, Gnoni A, Licchetta A, Delcuratolo S, Memeo R, Solimando AG, Argentiero A. Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma. Medicina. 2019; 55(10):698. https://doi.org/10.3390/medicina55100698
Chicago/Turabian StyleLongo, Vito, Oronzo Brunetti, Antonio Gnoni, Antonella Licchetta, Sabina Delcuratolo, Riccardo Memeo, Antonio Giovanni Solimando, and Antonella Argentiero. 2019. "Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma" Medicina 55, no. 10: 698. https://doi.org/10.3390/medicina55100698