Overview of Immune Checkpoint Inhibitors Therapy for Hepatocellular Carcinoma, and The ITA.LI.CA Cohort Derived Estimate of Amenability Rate to Immune Checkpoint Inhibitors in Clinical Practice
Abstract
:1. Introduction
2. Cancer Immunotherapy
3. Rationale of Immune Checkpoint Blockade in Hepatocellular Carcinoma
4. Strategies for Patients Selection
4.1. T-Cell Exhaustion
4.2. The Gut Microbiota
5. Outcome of Current Studies on Immunotherapy in Patients with HCC
5.1. Efficacy
5.2. Results of Monotherapy with Checkpoint Inhibitors in HCC
5.2.1. Tremelimumab
5.2.2. Nivolumab
5.2.3. Pembrolizumab
5.2.4. Camrelizumab
5.2.5. Tislelizumab
5.2.6. Durvalumab
5.3. Combination of Two Immune Checkpoint Inhibitors
5.3.1. Durvalumab plus Tremelimumab
5.3.2. Nivolumab plus Ipilimumab
5.4. Combination of Immune Checkpoint Inhibitors with Molecular-Targeted Agents
5.4.1. Atezolizumab plus Bevacizumab
5.4.2. Pembrolizumab plus Lenvatinib
5.4.3. Other Combinations
5.5. Immune Checkpoint Inhibitors as Neo-Adjuvant or Adjuvant Therapy, or in Combination with Local Treatments
6. Liver Involvement in Immune-Related-Adverse Events
7. Assessment of Treatment Response: The iRECIST Criteria
8. Rationale Underlying the Use of the ITA.LI.CA Database to Assess Real-Life Applicability of Checkpoint Inhibitors
8.1. First-Line Scenario
8.2. Second-Line Scenario
9. Conclusions
Funding
Conflicts of Interest
References
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NCT | Phase | Drug | Procedure | Line of Treatment | Primary End-Point | Estimated Study Completion Date | Company Conducting the Trial |
---|---|---|---|---|---|---|---|
NCT03298451 | III | Tremelilumab (+Durvalumab) vs Sorafenib | - | 1 | OS | 06/2021 | Astra Zeneca |
NCT02576509 | III | Nivolumab vs Sorafenib | - | 1 | OS | 07/2020 | BMS |
NCT03412773 | III | Tislelizumab vs Sorafenib | - | 1 | OS | 05/2022 | BeiGene |
NCT03062358 | III | Pembrolizumab vs placebo | - | 2 | OS | 01/2022 | MSD |
NCT02702401 | III | Pembrolizumab vs placebo | - | 2 | OS, PFS | 06/2020 | MSD |
NCT02702414 | II | Pembrolizumab | - | 1-2 | ORR | 05/2021 | MSD |
NCT02519348 | II | Tremelilumab (+Durvalumab) | - | 2 | Safety, DLT | 04/2021 | MedImmune LLC |
NCT03163992 | II | Pembrolizumab | - | 2 | ORR | 12/2020 | Samsung Medical Center |
NCT02658019 | II | Pembrolizumab | - | >2 | DCR, Safety | 11/2020 | Lynn Feun |
NCT03389126 | II | Avelumab | - | >2 | ORR | 03/2020 | Seoul National University Hospital |
NCT03419897 | II | Tislelizumab | - | >2 | ORR | 09/2021 | BeiGene |
NCT03033446 | II | Nivolumab | SIRT | Any | ORR | 12/2019 | National Cancer Centre, Singapore |
ign="middle" style="border-bottom:solid thin">1 | ORR | 11/2020 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | ||||
NCT02821754 | II | Tremelilumab | Local ablation | 1 | PFS | 04/2021 | National Cancer Institute (NCI) |
NCT03630640 | II | Nivolumab | Electroporation | 1 | RFS | 09/2020 | Assistance Publique—Hôpitaux de Paris |
NCT03482102 | II | Tremelilumab (+Durvalumab) | BRT | 2 | ORR | 10/2025 | Massachusetts General Hospital |
NCT03316872 | II | Pembrolizumab | SBRT | 2 | ORR | 04/2022 | University Health Network, Toronto |
NCT01658878 | IB/II | Nivolumab vs Sorafenib | - | 1 | ORR | 12/2019 | BMS |
NCT02423343 | IB/II | Nivolumab + Galunisertib | - | 2 | MTD, Safety | 12/2019 | Eli Lilly and Company |
NCT01658878 | IB/II | Nivolumab + Ipilimumab | - | >2 | ORR | 12/2019 | BMS |
NCT02940496 | I/II | Pembrolizumab | - | 2 | Biomarkers | 12/2019 | M.D. Anderson Cancer Center |
NCT03397654 | IB | Pembrolizumab | TACE | 1 | Safety | 12/2020 | Imperial College London |
NCT02837029 | I | Nivolumab | SIRT | Any | MTD | 07/2020 | Northwestern University |
NCT03099564 | I | Pembrolizumab | SIRT | 1 | PFS | 01/2020 | Autumn McRee, MD |
NCT03143270 | I | Nivolumab | debTACE | 1 | Safety | 04/2020 | Memorial Sloan Kettering Cancer Center |
NCT03203304 | I | Nivolumab/Ipilimumab | SBRT | 1 | Safety | 08/2020 | University of Chicago |
NCT01853618 | I | Tremelilumab | Local Ablation | 1 | Safety | 12/2020 | National Cancer Institute (NCI) |
ITA.LI.CA Database | Number of HCCs = 11,483 (including recurrences) | |
(A) First-step removal | 1. HCC diagnosis before 01/01/2008 = 3144 | |
2. HCC recurrence = 4453 | ||
Number of patients = 3886 (01/01/2008-31/12/2016) | ||
(B) Second step removal | Missing data = 1403 | |
Examined population = 2483 (100.0%) | ||
(C) Third step removal | Nivolumab | Pembrolizumab |
|
| |
Final population = 525/2483 (21.1%) | Final population = 268/2483 (10.8%) |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Giannini, E.G.; Aglitti, A.; Borzio, M.; Gambato, M.; Guarino, M.; Iavarone, M.; Lai, Q.; Levi Sandri, G.B.; Melandro, F.; Morisco, F.; et al. Overview of Immune Checkpoint Inhibitors Therapy for Hepatocellular Carcinoma, and The ITA.LI.CA Cohort Derived Estimate of Amenability Rate to Immune Checkpoint Inhibitors in Clinical Practice. Cancers 2019, 11, 1689. https://doi.org/10.3390/cancers11111689
Giannini EG, Aglitti A, Borzio M, Gambato M, Guarino M, Iavarone M, Lai Q, Levi Sandri GB, Melandro F, Morisco F, et al. Overview of Immune Checkpoint Inhibitors Therapy for Hepatocellular Carcinoma, and The ITA.LI.CA Cohort Derived Estimate of Amenability Rate to Immune Checkpoint Inhibitors in Clinical Practice. Cancers. 2019; 11(11):1689. https://doi.org/10.3390/cancers11111689
Chicago/Turabian StyleGiannini, Edoardo G., Andrea Aglitti, Mauro Borzio, Martina Gambato, Maria Guarino, Massimo Iavarone, Quirino Lai, Giovanni Battista Levi Sandri, Fabio Melandro, Filomena Morisco, and et al. 2019. "Overview of Immune Checkpoint Inhibitors Therapy for Hepatocellular Carcinoma, and The ITA.LI.CA Cohort Derived Estimate of Amenability Rate to Immune Checkpoint Inhibitors in Clinical Practice" Cancers 11, no. 11: 1689. https://doi.org/10.3390/cancers11111689