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First-line targ veted therapies of advanced hepatocellular carcinoma: A Bayesian network analysis of randomized controlled trials

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  • Wei Ding
  • Yulin Tan
  • Yan Qian
  • Wenbo Xue
  • Yibo Wang
  • Peng Jiang
  • Xuezhong Xu

Abstract

Purpose: A variety of targeted drug were developed and proved effective and safe in clinical trials. Our study aims to compare the efficacies and safety of different targeted drugs in advanced hepatocellular carcinoma (HCC) for first-line treatment using a Bayesian network meta-analysis approach. Methods: PubMed, Embase, and Cochrane library were searched for randomized controlled trials (RCTs) of advanced HCC patients that treated with different targeted drugs. Time to progress (TTP), overall survival (OS) and progress-free survival (PFS) were calculated as hazard ratios (HRs). Objective response rate (ORR) and the proportion of Grade 3–5 adverse events (G3-5AE) were expressed as odds ratios (ORs). We pooled study-specific HRs and ORs using Bayesian network meta-analyses, and ranked first-line drugs by the surface under the cumulative ranking curve (SUCRA). Results: A total of 22 RCTs with 9288 patients were enrolled. Brivanib, linifanib, lenvatinib and sorafenib showed a significant improvement on TTP compared to placebo (HR range, 0.45–0.72). Sunitinib (HR = 1.99) and nintedanib (HR = 2.17) showed a significant decline on TTP compared to lenvatinib. Vandetanib (HR = 0.44) and sorafenib (HR = 0.73) showed a significant improvement on OS compared to placebo. There was no significant difference in PFS, ORR and G3-5AE across different drugs. According to cluster rank analysis, vandetanib was the drug with both more effective (OS) and more secure (G3-5AE) compared to Sor followed by nintedanib. Conclusions: This network meta-analysis shows that vandetanib, linifanib, lenvatinib and nintedanib potentially may be the best substitution of sorafenib against advanced HCC as first-line targeted drugs. Vandetanib seems to be the best choise with low quality of evidence. For better survival, novel targeted treatment options for HCC are sorely needed.

Suggested Citation

  • Wei Ding & Yulin Tan & Yan Qian & Wenbo Xue & Yibo Wang & Peng Jiang & Xuezhong Xu, 2020. "First-line targ veted therapies of advanced hepatocellular carcinoma: A Bayesian network analysis of randomized controlled trials," PLOS ONE, Public Library of Science, vol. 15(3), pages 1-19, March.
    • Handle: RePEc:plo:pone00:0229492
    DOI: 10.1371/journal.pone.0229492
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    References listed on IDEAS

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    1. Sofia Dias & Alex J. Sutton & Nicky J. Welton & A. E. Ades, 2013. "Evidence Synthesis for Decision Making 3," Medical Decision Making, , vol. 33(5), pages 618-640, July.
    2. Sofia Dias & Nicky J. Welton & Alex J. Sutton & A. E. Ades, 2013. "Evidence Synthesis for Decision Making 5," Medical Decision Making, , vol. 33(5), pages 657-670, July.
    3. Sofia Dias & Alex J. Sutton & A. E. Ades & Nicky J. Welton, 2013. "Evidence Synthesis for Decision Making 2," Medical Decision Making, , vol. 33(5), pages 607-617, July.
    4. Sofia Dias & Nicky J. Welton & Alex J. Sutton & Deborah M. Caldwell & Guobing Lu & A. E. Ades, 2013. "Evidence Synthesis for Decision Making 4," Medical Decision Making, , vol. 33(5), pages 641-656, July.
    5. Georgia Salanti & Cinzia Del Giovane & Anna Chaimani & Deborah M Caldwell & Julian P T Higgins, 2014. "Evaluating the Quality of Evidence from a Network Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-14, July.
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