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Alternative treatment strategies to sorafenib in patients with advanced hepatocellular carcinoma: a meta-analysis of randomized Phase III trials

Authors Wang H, Wang HF, Yu ZC, Liu HH

Received 22 April 2018

Accepted for publication 15 June 2018

Published 27 August 2018 Volume 2018:11 Pages 5195—5201


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche

Hui Wang, Hefang Wang, Zhichong Yu, Honghao Liu

Department of Radiation Oncology, Yancheng First People’s Hospital, Yancheng, Jiangsu 224005, China

Introduction: This meta-analysis was conducted to evaluate efficacy and safety in patients treated with sorafenib vs other tyrosine-kinase inhibitors (TKIs) or selective internal radiotherapy (SIRT) for advanced hepatocellular carcinoma (HCC).
Methods: Electronic databases were systematically reviewed for randomized Phase III trials comparing sorafenib with other TKIs or SIRT in advanced HCC. Sorafenib was defined as the control arm. Other TKIs or SIRT was defined as the experimental arm. Overall survival (OS), time to progression (TTP), objective response rate (ORR), disease-control rate (DCR), and adverse events (AEs) were reviewed. Four trials in the other-TKI group (n=4,218) and two in the SIRT group (n=819) were eligible.
Results: Compared with sorafenib, other TKIs showed similar benefit on OS (HR 1.08, 95% CI 0.93–1.24; P=0.31) and TTP (HR 0.86, 95% CI 0.66–1.12; P=0.26) for advanced HCC. A significant increase in ORR (RR 1.67, 95% CI 1.15–2.43; P=0.008) was found with other TKIs, but no increase in DCR (RR 1.11, 95% CI 0.98–1.26; P=0.11) was observed. Other TKIs were associated with more frequent grade 3/4 AEs than sorafenib, including hypertension (P<0.00001), thrombocytopenia (P=0.002), fatigue (P<0.00001), decreased appetite (P<0.00001), and vomiting (P<0.0001). For locally advanced HCC, neither OS (HR 1.14, 95% CI 0.98–1.32; P=0.09) nor TTP (HR 0.87, 95% CI 0.74–1.02; P=0.10) differed significantly in SIRT and sorafenib. There was an increase in ORR (RR 2.60, 95% CI 1.69–4.00; P<0.0001), but no improvement in DCR (RR 0.91, 95% CI 0.81–1.02; P=0.11) in the SIRT group. Fewer patients treated with SIRT had grade 3/4 AEs than those treated with sorafenib, including diarrhea (P<0.0001), fatigue (P=0.0006), and hand–foot syndrome (P=0.0002). Other TKIs were noninferior to sorafenib in OS and TTP in advanced HCC, but with increased risk of toxicities.
Conclusion: Patients with locally advanced HCC treated with SIRT got similar efficacy with less toxicity to those treated with sorafenib.

Keywords: sorafenib, tyrosine-kinase inhibitors, selective internal radiotherapy, hepatocellular carcinoma, meta-analysis

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