Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials
Robin Park,1 Laercio Lopes da Silva,1 Voravech Nissaisorakarn,1 Ivy Riano,1 Stephen Williamson,2 Weijing Sun,2 Anwaar Saeed2 1Department of Medicine, MetroWest Medical Center/Tufts University School of Medicine, Framingham, MA, USA; 2Department of Medicine, Division of Medical Oncology, Kansas Unive...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-03-01
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| Series: | Journal of Hepatocellular Carcinoma |
| Subjects: | |
| Online Access: | https://www.dovepress.com/comparison-of-efficacy-of-systemic-therapies-in-advanced-hepatocellula-peer-reviewed-article-JHC |
| _version_ | 1818741963779735552 |
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| author | Park R Lopes da Silva L Nissaisorakarn V Riano I Williamson S Sun W Saeed A |
| author_facet | Park R Lopes da Silva L Nissaisorakarn V Riano I Williamson S Sun W Saeed A |
| author_sort | Park R |
| collection | DOAJ |
| description | Robin Park,1 Laercio Lopes da Silva,1 Voravech Nissaisorakarn,1 Ivy Riano,1 Stephen Williamson,2 Weijing Sun,2 Anwaar Saeed2 1Department of Medicine, MetroWest Medical Center/Tufts University School of Medicine, Framingham, MA, USA; 2Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, KS, USACorrespondence: Anwaar SaeedKansas University Cancer Center, GI Oncology Program, Kansas City, KS, USAEmail asaeed@kumc.eduBackground: Several systemic agents have been approved for use in advanced hepatocellular carcinoma (aHCC). However, it is unclear which treatment is superior in either the first- or second-line settings due to the paucity of head-to-head comparative trials. Therefore, we have conducted a systematic review and network meta-analysis for the indirect comparison of the systemic agents in the first line and second line settings.Methods: Randomized clinical trials evaluating systemic agents in first and second line settings in aHCC from inception to April 2020 were identified by searching PubMed, EMBASE, and Cochrane Databases and the annual ASCO and ESMO conferences from 2017 to 2020. Studies in English reporting clinical outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were included. The primary outcomes of interest were pooled hazard ratios (HR) of OS and pooled odds ratios (OR) of ORR in first line studies and pooled HR of PFS and OR of ORR for second line studies. Additionally, OS for second line agents were reported in the qualitative analysis.Results: Overall, first line studies comprised 8335 patients (13 studies) and second line studies comprised 4612 patients (11 studies). In the first line setting, atezolizumab plus bevacizumab was associated with the highest OS benefit over sorafenib (HR 0.58, 95% CI, 0.42– 0.80; P-score 0.993). Additionally, lenvatinib was associated with the greatest ORR benefit (OR 3.34, 95% CI, 2.17– 5.14; P-score 0.080) in the first line setting. In the second line setting, cabozantinib was associated with the highest PFS benefit over placebo (HR 0.44, 95% CI, 0.29– 0.66; P-score 0.854) as well as the highest ORR benefit (OR 9.40, 95% CI, 1.25– 70.83, P-score, 0.266).Conclusion: Atezolizumab plus bevacizumab appears to have superior efficacy among first line agents whereas cabozantinib appears to be superior in the second line setting. Further studies are warranted to determine whether the type of prior therapy received affects the efficacy of subsequent second line therapy.Keywords: advanced hepatocellular carcinoma, targeted therapy, immunotherapy, systemic therapy |
| first_indexed | 2024-12-18T02:04:59Z |
| format | Article |
| id | doaj.art-b0302954f7924bf795ec8ecc28697f10 |
| institution | Directory Open Access Journal |
| issn | 2253-5969 |
| language | English |
| last_indexed | 2024-12-18T02:04:59Z |
| publishDate | 2021-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Hepatocellular Carcinoma |
| spelling | doaj.art-b0302954f7924bf795ec8ecc28697f102022-12-21T21:24:38ZengDove Medical PressJournal of Hepatocellular Carcinoma2253-59692021-03-01Volume 814515463307Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled TrialsPark RLopes da Silva LNissaisorakarn VRiano IWilliamson SSun WSaeed ARobin Park,1 Laercio Lopes da Silva,1 Voravech Nissaisorakarn,1 Ivy Riano,1 Stephen Williamson,2 Weijing Sun,2 Anwaar Saeed2 1Department of Medicine, MetroWest Medical Center/Tufts University School of Medicine, Framingham, MA, USA; 2Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, KS, USACorrespondence: Anwaar SaeedKansas University Cancer Center, GI Oncology Program, Kansas City, KS, USAEmail asaeed@kumc.eduBackground: Several systemic agents have been approved for use in advanced hepatocellular carcinoma (aHCC). However, it is unclear which treatment is superior in either the first- or second-line settings due to the paucity of head-to-head comparative trials. Therefore, we have conducted a systematic review and network meta-analysis for the indirect comparison of the systemic agents in the first line and second line settings.Methods: Randomized clinical trials evaluating systemic agents in first and second line settings in aHCC from inception to April 2020 were identified by searching PubMed, EMBASE, and Cochrane Databases and the annual ASCO and ESMO conferences from 2017 to 2020. Studies in English reporting clinical outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were included. The primary outcomes of interest were pooled hazard ratios (HR) of OS and pooled odds ratios (OR) of ORR in first line studies and pooled HR of PFS and OR of ORR for second line studies. Additionally, OS for second line agents were reported in the qualitative analysis.Results: Overall, first line studies comprised 8335 patients (13 studies) and second line studies comprised 4612 patients (11 studies). In the first line setting, atezolizumab plus bevacizumab was associated with the highest OS benefit over sorafenib (HR 0.58, 95% CI, 0.42– 0.80; P-score 0.993). Additionally, lenvatinib was associated with the greatest ORR benefit (OR 3.34, 95% CI, 2.17– 5.14; P-score 0.080) in the first line setting. In the second line setting, cabozantinib was associated with the highest PFS benefit over placebo (HR 0.44, 95% CI, 0.29– 0.66; P-score 0.854) as well as the highest ORR benefit (OR 9.40, 95% CI, 1.25– 70.83, P-score, 0.266).Conclusion: Atezolizumab plus bevacizumab appears to have superior efficacy among first line agents whereas cabozantinib appears to be superior in the second line setting. Further studies are warranted to determine whether the type of prior therapy received affects the efficacy of subsequent second line therapy.Keywords: advanced hepatocellular carcinoma, targeted therapy, immunotherapy, systemic therapyhttps://www.dovepress.com/comparison-of-efficacy-of-systemic-therapies-in-advanced-hepatocellula-peer-reviewed-article-JHCadvanced hepatocellular carcinomatargeted therapyimmunotherapysystemic therapy. |
| spellingShingle | Park R Lopes da Silva L Nissaisorakarn V Riano I Williamson S Sun W Saeed A Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials Journal of Hepatocellular Carcinoma advanced hepatocellular carcinoma targeted therapy immunotherapy systemic therapy. |
| title | Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials |
| title_full | Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials |
| title_fullStr | Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials |
| title_full_unstemmed | Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials |
| title_short | Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials |
| title_sort | comparison of efficacy of systemic therapies in advanced hepatocellular carcinoma updated systematic review and frequentist network meta analysis of randomized controlled trials |
| topic | advanced hepatocellular carcinoma targeted therapy immunotherapy systemic therapy. |
| url | https://www.dovepress.com/comparison-of-efficacy-of-systemic-therapies-in-advanced-hepatocellula-peer-reviewed-article-JHC |
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