Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials
Background & Aims: Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic treatments for hepatocellular carcinoma in terms of overall survival (OS), progre...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | JHEP Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923000332 |
| _version_ | 1797838538875600896 |
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| author | Claudia Angela Maria Fulgenzi Bernhard Scheiner James Korolewicz Charalampos-Vlasios Stikas Alessandra Gennari Bruno Vincenzi Mark R. Openshaw Marianna Silletta Matthias Pinter Alessio Cortellini Lorenza Scotti Antonio D’Alessio David J. Pinato |
| author_facet | Claudia Angela Maria Fulgenzi Bernhard Scheiner James Korolewicz Charalampos-Vlasios Stikas Alessandra Gennari Bruno Vincenzi Mark R. Openshaw Marianna Silletta Matthias Pinter Alessio Cortellini Lorenza Scotti Antonio D’Alessio David J. Pinato |
| author_sort | Claudia Angela Maria Fulgenzi |
| collection | DOAJ |
| description | Background & Aims: Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic treatments for hepatocellular carcinoma in terms of overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate, and incidence of adverse events (AEs). Methods: After performing a literature review from January 2008 to September 2022, we screened 6,329 studies and reviewed 3,009 studies, leading to identification of 15 phase III trials for analysis. We extracted odds ratios for objective response rate and disease control rate, relative risks for AEs, and hazard ratios (HRs) with 95% CIs for OS and PFS, and used a frequentist network metanalysis, with fixed-effect multivariable meta-regression models to estimate the indirect pooled HRs, odds ratios, relative risks, and corresponding 95% CIs, considering sorafenib as reference. Results: Of 10,820 included patients, 10,444 received active treatment and 376 placebo. Sintilimab + IBI350, camrelizumab + rivoceranib, and atezolizumab + bevacizumab provided the greatest reduction in the risk of death compared with sorafenib, with HRs of 0.57 (95% CI 0.43–0.75), 0.62 (95% CI 0.49–0.79), and 0.66 (95% CI 0.52–0.84), respectively. Considering PFS, camrelizumab + rivoceranib and pembrolizumab + lenvatinib were associated with the greatest reduction in the risk of PFS events compared with sorafenib, with HRs of 0.52 (95% CI 0.41–0.65) and 0.52 (95% CI 0.35–0.77), respectively. Immune checkpoint inhibitor (ICI) monotherapies carried the lowest risk for all-grade and grade ≥3 AEs. Conclusions: The combinations of ICI + anti-vascular endothelial growth factor, and double ICIs lead to the greatest OS benefit compared with sorafenib, whereas ICI + kinase inhibitor regimens are associated with greater PFS benefit at the cost of higher toxicity rates. Impact and Implications: In the last few years, many different therapies have been studied for patients with primary liver cancer that cannot be treated with surgery. In these cases, anticancer drugs (alone or in combination) are given with the intent to keep the cancer at bay and, ultimately, to prolong survival. Among all the therapies that have been investigated, the combination of immunotherapy (drugs that boost the immune system against the cancer) and anti-angiogenic agents (drugs that act on tumoural vessels) has appeared the best to improve survival. Similarly, the combination of two types of immunotherapies that activate the immune system at different levels has also shown positive results. Systematic Review Registration: PROSPERO CRD42022366330. |
| first_indexed | 2024-04-09T15:43:33Z |
| format | Article |
| id | doaj.art-da5bfd6a88df4c8ca1113b3b4099192a |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-04-09T15:43:33Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-da5bfd6a88df4c8ca1113b3b4099192a2023-04-27T06:07:41ZengElsevierJHEP Reports2589-55592023-05-0155100702Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trialsClaudia Angela Maria Fulgenzi0Bernhard Scheiner1James Korolewicz2Charalampos-Vlasios Stikas3Alessandra Gennari4Bruno Vincenzi5Mark R. Openshaw6Marianna Silletta7Matthias Pinter8Alessio Cortellini9Lorenza Scotti10Antonio D’Alessio11David J. Pinato12Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK; Medical Oncology Department, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, AustriaDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UKDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UKDivision of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyMedical Oncology Department, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyUniversity Hospitals Birmingham Cancer Centre, Birmingham, UKMedical Oncology Department, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, AustriaDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK; Medical Oncology Department, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyDepartment of Translational Medicine, Università del Piemonte Orientale UPO, Novara, ItalyDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK; Department of Biomedical Sciences, Humanitas University, Milan, ItalyDepartment of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK; Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy; Corresponding author. Address: Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, W12 0HS, London, UK. Tel.: +44-020-83833720Background & Aims: Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic treatments for hepatocellular carcinoma in terms of overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate, and incidence of adverse events (AEs). Methods: After performing a literature review from January 2008 to September 2022, we screened 6,329 studies and reviewed 3,009 studies, leading to identification of 15 phase III trials for analysis. We extracted odds ratios for objective response rate and disease control rate, relative risks for AEs, and hazard ratios (HRs) with 95% CIs for OS and PFS, and used a frequentist network metanalysis, with fixed-effect multivariable meta-regression models to estimate the indirect pooled HRs, odds ratios, relative risks, and corresponding 95% CIs, considering sorafenib as reference. Results: Of 10,820 included patients, 10,444 received active treatment and 376 placebo. Sintilimab + IBI350, camrelizumab + rivoceranib, and atezolizumab + bevacizumab provided the greatest reduction in the risk of death compared with sorafenib, with HRs of 0.57 (95% CI 0.43–0.75), 0.62 (95% CI 0.49–0.79), and 0.66 (95% CI 0.52–0.84), respectively. Considering PFS, camrelizumab + rivoceranib and pembrolizumab + lenvatinib were associated with the greatest reduction in the risk of PFS events compared with sorafenib, with HRs of 0.52 (95% CI 0.41–0.65) and 0.52 (95% CI 0.35–0.77), respectively. Immune checkpoint inhibitor (ICI) monotherapies carried the lowest risk for all-grade and grade ≥3 AEs. Conclusions: The combinations of ICI + anti-vascular endothelial growth factor, and double ICIs lead to the greatest OS benefit compared with sorafenib, whereas ICI + kinase inhibitor regimens are associated with greater PFS benefit at the cost of higher toxicity rates. Impact and Implications: In the last few years, many different therapies have been studied for patients with primary liver cancer that cannot be treated with surgery. In these cases, anticancer drugs (alone or in combination) are given with the intent to keep the cancer at bay and, ultimately, to prolong survival. Among all the therapies that have been investigated, the combination of immunotherapy (drugs that boost the immune system against the cancer) and anti-angiogenic agents (drugs that act on tumoural vessels) has appeared the best to improve survival. Similarly, the combination of two types of immunotherapies that activate the immune system at different levels has also shown positive results. Systematic Review Registration: PROSPERO CRD42022366330.http://www.sciencedirect.com/science/article/pii/S2589555923000332Targeted therapyTyrosine kinase inhibitorsImmune checkpoint inhibitorsFirst-line treatmentLiver cancer |
| spellingShingle | Claudia Angela Maria Fulgenzi Bernhard Scheiner James Korolewicz Charalampos-Vlasios Stikas Alessandra Gennari Bruno Vincenzi Mark R. Openshaw Marianna Silletta Matthias Pinter Alessio Cortellini Lorenza Scotti Antonio D’Alessio David J. Pinato Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials JHEP Reports Targeted therapy Tyrosine kinase inhibitors Immune checkpoint inhibitors First-line treatment Liver cancer |
| title | Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials |
| title_full | Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials |
| title_fullStr | Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials |
| title_full_unstemmed | Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials |
| title_short | Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials |
| title_sort | efficacy and safety of frontline systemic therapy for advanced hcc a network meta analysis of landmark phase iii trials |
| topic | Targeted therapy Tyrosine kinase inhibitors Immune checkpoint inhibitors First-line treatment Liver cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923000332 |
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