Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis
BackgroundHepatocellular carcinoma (HCC) is the third most fatal cancer, with a 5-year survival rate of 18%. Standard frontline-therapy is multikinase inhibitors (MKIs), but accessibility is still limited, particularly in developing countries. This network meta-analysis (NMA) aimed to compare the ef...
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doaj-ef31e70e8d784758b108919fa1a1d80e2021-03-31T06:04:51ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.654020654020Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-AnalysisSongporn Oranratnachai0Songporn Oranratnachai1Sasivimol Rattanasiri2Anantaporn Pooprasert3Amarit Tansawet4Amarit Tansawet5Thanyanan Reungwetwattana6John Attia7Ammarin Thakkinstian8Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandOncology Clinic, Sriphat Medical Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandDepartment of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandOncology Unit, Division of Internal Medicine, Uttaradit Hospital, Uttaradit, ThailandDepartment of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Surgery, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, ThailandDivision of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCentre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, AustraliaDepartment of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandBackgroundHepatocellular carcinoma (HCC) is the third most fatal cancer, with a 5-year survival rate of 18%. Standard frontline-therapy is multikinase inhibitors (MKIs), but accessibility is still limited, particularly in developing countries. This network meta-analysis (NMA) aimed to compare the efficacy of usual chemotherapy vs MKIs.MethodRandomised-controlled trials (RCTs) comparing any among chemotherapy vs MKIs in treatment-naïve patients with advanced HCCs were identified from MEDLINE and SCOPUS databases. Overall survival (OS) and progression-free survival (PFS) probabilities and times were extracted from Kaplan-Meier curves using Digitizer, and then converted to individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate median OS and PFS. A two-stage NMA was applied for the overall response rate and adverse events (AEs) outcome.ResultsA total of 20 RCTs were eligible for NMA. Lenvatinib was the best treatment among single MKIs, with median OS and PFS of 9 and 6.3 months, without significant differences in AEs relative to other MKIs. Median OS and PFS were 0.70 (-0.42, 1.83) and 2.17 (1.41, 2.93) months longer with Lenvatinib than Sorafenib. Among chemotherapy agents, FOLFOX4 had the longest median OS and PFS at 7.9 and 4.3 months, respectively, without significant AEs compared to other chemotherapies. The combination of Sorafenib+Doxorubicin prolonged median OS and PFS to 12.7 and 6.3 months, respectively.ConclusionUse of the MKIs Lenvatinib or Sorafenib as first line systemic treatment for advanced HCC could be beneficial. However, FOLFOX4 might be the optimal choice in a developing country where the health-care budget is limited.https://www.frontiersin.org/articles/10.3389/fonc.2021.654020/fullchemotherapyfirst-line systemic treatmenthepatocellular carcinomamultikinase inhibitorsnetwork meta-analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Songporn Oranratnachai Songporn Oranratnachai Sasivimol Rattanasiri Anantaporn Pooprasert Amarit Tansawet Amarit Tansawet Thanyanan Reungwetwattana John Attia Ammarin Thakkinstian |
spellingShingle |
Songporn Oranratnachai Songporn Oranratnachai Sasivimol Rattanasiri Anantaporn Pooprasert Amarit Tansawet Amarit Tansawet Thanyanan Reungwetwattana John Attia Ammarin Thakkinstian Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis Frontiers in Oncology chemotherapy first-line systemic treatment hepatocellular carcinoma multikinase inhibitors network meta-analysis |
author_facet |
Songporn Oranratnachai Songporn Oranratnachai Sasivimol Rattanasiri Anantaporn Pooprasert Amarit Tansawet Amarit Tansawet Thanyanan Reungwetwattana John Attia Ammarin Thakkinstian |
author_sort |
Songporn Oranratnachai |
title |
Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis |
title_short |
Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis |
title_full |
Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis |
title_fullStr |
Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis |
title_full_unstemmed |
Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis |
title_sort |
efficacy of first line systemic chemotherapy and multikinase inhibitors in advanced hepatocellular carcinoma: a systematic review and network meta-analysis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-03-01 |
description |
BackgroundHepatocellular carcinoma (HCC) is the third most fatal cancer, with a 5-year survival rate of 18%. Standard frontline-therapy is multikinase inhibitors (MKIs), but accessibility is still limited, particularly in developing countries. This network meta-analysis (NMA) aimed to compare the efficacy of usual chemotherapy vs MKIs.MethodRandomised-controlled trials (RCTs) comparing any among chemotherapy vs MKIs in treatment-naïve patients with advanced HCCs were identified from MEDLINE and SCOPUS databases. Overall survival (OS) and progression-free survival (PFS) probabilities and times were extracted from Kaplan-Meier curves using Digitizer, and then converted to individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate median OS and PFS. A two-stage NMA was applied for the overall response rate and adverse events (AEs) outcome.ResultsA total of 20 RCTs were eligible for NMA. Lenvatinib was the best treatment among single MKIs, with median OS and PFS of 9 and 6.3 months, without significant differences in AEs relative to other MKIs. Median OS and PFS were 0.70 (-0.42, 1.83) and 2.17 (1.41, 2.93) months longer with Lenvatinib than Sorafenib. Among chemotherapy agents, FOLFOX4 had the longest median OS and PFS at 7.9 and 4.3 months, respectively, without significant AEs compared to other chemotherapies. The combination of Sorafenib+Doxorubicin prolonged median OS and PFS to 12.7 and 6.3 months, respectively.ConclusionUse of the MKIs Lenvatinib or Sorafenib as first line systemic treatment for advanced HCC could be beneficial. However, FOLFOX4 might be the optimal choice in a developing country where the health-care budget is limited. |
topic |
chemotherapy first-line systemic treatment hepatocellular carcinoma multikinase inhibitors network meta-analysis |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.654020/full |
work_keys_str_mv |
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