Identifying Optimal Therapies in Patients with Advanced Hepatocellular Carcinoma: a Systematic Review and Network Meta-analysis

Overview

Journal Transl Gastroenterol Hepatol

Publisher AME Publishing Company

Specialty Gastroenterology

Date 2022 Oct 27

PMID 36300147

Authors

Zhenyu Yang

Yao Tong

Lin Yang

Xianli He

Guoqiang Bao

Xilin Du

Affiliations

Soon will be listed here.

Abstract

Background: Recently, increasing literature has been reported on optimal therapies in patients with advanced hepatocellular carcinoma (HCC) and many therapeutic modalities have been proposed to improve the survival rate. However, the results are not consistent due to different research protocols, small sample sizes and different study endpoints and there is no standard treatment protocol has been defined. Therefore, it is very important to explore the optimal bonding mode and to evaluate the efficacy and safety of the optimal sequential therapy for those patients.

Methods: We searched available databases through January 2020 for relevant studies. The main outcome measure was 1-year overall survival (OS) and overall response rate (ORR); the secondary outcome measure was a composite of toxic effects retrieved grade 3 or 4 adverse events (AEs) from all included studies. Statistical analyses were conducted using STATA version 15 and GeMTC package in the R statistical software.

Results: After a detailed review, 8 randomized controlled trials (RCTs) and 20 retrospective studies involving 3,675 advanced HCC patients were included for network meta-analysis. Indirect comparisons showed that hepatic arterial infusion chemotherapy (HAIC) plus radiofrequency ablation (RFA) was highest probability of obtaining the best OS rate of 1 year [surface under the cumulative ranking (SUCRA), 0.95] and ORR (SUCRA, 0.86) when compared with other potential optimal therapies and which had ranked the first in all treatment regimens, followed by HAIC (SUCRA, 0.75). Direct and indirect comparison of 1-year OS and ORR with all treatment regimens each other showed that for all treatment regimens, patients showed significant clinical benefit when compared with transcatheter arterial chemoembolization (TACE) or sorafenib alone. However, the incidence of treatment-related AEs of grade 3 or 4 occurred in patients who have received targeted drug sorafenib therapy (SUCRA, 0.51) compared with other interesting regimens.

Conclusions: HAIC may be a valuable therapeutic strategy for advanced HCC patients to prevent recurrence and metastasis after RFA, as well as in improving patient prognosis and quality of life. Meanwhile, HAIC combined with RFA is a safe and effective treatment in patients with advanced HCC, and this combination therapy can significantly prolong 1-year survival rate when compared with other optimal sequential therapies.

Trial Registration: This study is registered with PROSPERO, number CRD42020176149.

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References

Llovet J, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-90. DOI: 10.1056/NEJMoa0708857. View

Zhang Z, Liu Q, Zhang W, Ma J, Wang J, Luo J . Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus. World J Gastroenterol. 2017; 23(43):7735-7745. PMC: 5703933. DOI: 10.3748/wjg.v23.i43.7735. View

Wada Y, Takami Y, Matsushima H, Tateishi M, Ryu T, Yoshitomi M . The Safety and Efficacy of Combination Therapy of Sorafenib and Radiotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Study. Intern Med. 2017; 57(10):1345-1353. PMC: 5995712. DOI: 10.2169/internalmedicine.9826-17. View

Chow P, Gandhi M, Tan S, Khin M, Khasbazar A, Ong J . SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma. J Clin Oncol. 2018; 36(19):1913-1921. DOI: 10.1200/JCO.2017.76.0892. View

Gandhi M, Choo S, Thng C, Tan S, Low A, Cheow P . Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial. BMC Cancer. 2016; 16(1):856. PMC: 5100089. DOI: 10.1186/s12885-016-2868-y. View

Cainap C, Qin S, Huang W, Chung I, Pan H, Cheng Y . Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol. 2014; 33(2):172-9. PMC: 4279237. DOI: 10.1200/JCO.2013.54.3298. View

Uka K, Aikata H, Takaki S, Miki D, Kawaoka T, Jeong S . Pretreatment predictor of response, time to progression, and survival to intraarterial 5-fluorouracil/interferon combination therapy in patients with advanced hepatocellular carcinoma. J Gastroenterol. 2007; 42(10):845-53. DOI: 10.1007/s00535-007-2099-8. View

Yuan H, Lan Y, Li X, Tang J, Liu F . Large hepatocellular carcinoma with local remnants after transarterial chemoembolization: treatment by sorafenib combined with radiofrequency ablation or sorafenib alone. Am J Cancer Res. 2019; 9(4):791-799. PMC: 6511642. View

Hu H, Duan Z, Long X, Hertzanu Y, Shi H, Liu S . Sorafenib combined with transarterial chemoembolization versus transarterial chemoembolization alone for advanced-stage hepatocellular carcinoma: a propensity score matching study. PLoS One. 2014; 9(5):e96620. PMC: 4016022. DOI: 10.1371/journal.pone.0096620. View

10.

Feng R, Zong Y, Cao S, Xu R . Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?. Cancer Commun (Lond). 2019; 39(1):22. PMC: 6487510. DOI: 10.1186/s40880-019-0368-6. View

11.

Ando E, Tanaka M, Yamashita F, Kuromatsu R, Yutani S, Fukumori K . Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases. Cancer. 2002; 95(3):588-95. DOI: 10.1002/cncr.10694. View

12.

Zhu K, Chen J, Lai L, Meng X, Zhou B, Huang W . Hepatocellular carcinoma with portal vein tumor thrombus: treatment with transarterial chemoembolization combined with sorafenib--a retrospective controlled study. Radiology. 2014; 272(1):284-93. DOI: 10.1148/radiol.14131946. View

13.

Jeong S, Jang J, Lee J, Lee S, Kim S, Cha S . The efficacy of hepatic arterial infusion chemotherapy as an alternative to sorafenib in advanced hepatocellular carcinoma. Asia Pac J Clin Oncol. 2012; 8(2):164-71. DOI: 10.1111/j.1743-7563.2012.01543.x. View

14.

Obi S, Yoshida H, Toune R, Unuma T, Kanda M, Sato S . Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer. 2006; 106(9):1990-7. DOI: 10.1002/cncr.21832. View

15.

Cheng A, Kang Y, Chen Z, Tsao C, Qin S, Kim J . Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2008; 10(1):25-34. DOI: 10.1016/S1470-2045(08)70285-7. View

16.

Fujino H, Kimura T, Aikata H, Miyaki D, Kawaoka T, Kan H . Role of 3-D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. Hepatol Res. 2014; 45(6):607-17. DOI: 10.1111/hepr.12392. View

17.

Kudo M, Imanaka K, Chida N, Nakachi K, Tak W, Takayama T . Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 2011; 47(14):2117-27. DOI: 10.1016/j.ejca.2011.05.007. View

18.

Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca A, Pageaux G . Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017; 18(12):1624-1636. DOI: 10.1016/S1470-2045(17)30683-6. View

19.

Yuan J, Yin X, Tang B, Ma H, Zhang L, Li L . Transarterial Chemoembolization (TACE) Combined with Sorafenib in Treatment of HBV Background Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Propensity Score Matching Study. Biomed Res Int. 2019; 2019:2141859. PMC: 6699376. DOI: 10.1155/2019/2141859. View

20.

Ishida K, Hirooka M, Hiraoka A, Kumagi T, Uehara T, Hiasa Y . Treatment of hepatocellular carcinoma using arterial chemoembolization with degradable starch microspheres and continuous arterial infusion of 5-fluorouracil. Jpn J Clin Oncol. 2008; 38(9):596-603. DOI: 10.1093/jjco/hyn076. View