A comparison of transcatheter arterial chemoembolization used with and without apatinib for intermediate- to advanced-stage hepatocellular carcinoma: a systematic review and meta-analysis

Abstract

Background: Hepatocellular carcinoma (HCC) is a common cancer worldwide and prognosis for patients with the disease remains poor. Most patients are diagnosed at an advanced stage and are only eligible for palliative therapy. As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), apatinib has a certain antitumor effect for a variety of solid tumors. In clinical practice, clinicians have attempted to treat intermediate-to advanced-stage HCC patients with a combination of transcatheter arterial chemoembolization (TACE) and apatinib. However, a consensus on the therapeutic effects of this treatment is yet to be reached. This meta-analysis was conducted to compare the therapeutic efficacy and clinical safety of the combination therapy of TACE plus apatinib with that of TACE alone in patients with intermediate-to advanced-stage HCC.Methods: Relevant studies were identified by searching PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP) and the reference lists of retrieved articles up to July 31, 2019. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the therapeutic effects of TACE plus apatinib versus TACE on survival, objective response rate, disease control rate, progressive disease rate and adverse events using a mixed-effect model.Subgroup analyses of study type, dosage of apatinib, TACE regimen, study sample size between treatment groups and control groups were performed. Publication bias was assessed using fail-safe N, Begg-Mazumdar test and Egger's test.Results: From 23 eligible studies, a total of 1,342 patients were included in this review and meta-analysis. Among these studies, 18 were randomized clinical trials and 5 were case-control studies. Compared with those being treated with TACE alone, patients receiving TACE plus apatinib showed significantly better half-year survival (OR, 2.741, 95% CI, 1.745-4.306) and 1-year survival (OR, 2.284, 95% CI, 1.442-3.620).The superiority of TACE and apatinib over TACE monotherapy was evident in the disease control rate (OR, 2.919, 95% CI, 2.184-3.903), objective response rate (OR, 2.683, 95% CI, 2.099-3.429) and progressive disease rate (OR, 0.341, 95% CI, 0.255-0.456), respectively.

Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway

“…HCC incidence has shown a global upward trend over the last decade ( Bertuccio et al, 2017 ), with approximately over 60% patients at an intermediate or advanced stage when newly diagnosed ( Yang et al, 2019 ). For this portion of patients, TACE or systemic treatment combined with targeted molecular inhibitors would yield better outcomes; for instance, multi-targeted tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib have benefited patients with advanced and unresectable HCC ( Forner et al, 2018 ; Yamada et al, 2020 ; Yoo et al, 2020 ; Zhao et al, 2020 ). Due to the shortcomings of chemotherapeutic agents for HCC, for example low response, intolerable side effects, and severe toxicity, it remains necessary to discover a novel agent or an optimized therapy for HCC.…”

“…Unfortunately, its incidence and mortality rate have kept rising in the latest decade, despite the advances in preventive measures, screening techniques, and diagnostic and therapeutic technologies ( Balogh et al, 2016 ; Hashim et al, 2016 ). Besides hepatic resection, liver transplantation and local ablation, transarterial chemoembolization (TACE) combined with radiotherapy, sorafenib, or chemotherapeutic agents (anthracyclines, mitomycin, and cisplatin) is commonly employed for patients with HCC as a liver-directed therapy ( Zhao et al, 2016 ; Kim and Den Abbeele, 2019 ; Zhao et al, 2020 ). However, HCC is usually resistant to chemotherapeutic agents in TACE or system chemotherapy ( Bruix et al, 2016 ).…”

Transarterial chemoembolization (TACE) combined with apatinib versus TACE combined with sorafenib in advanced hepatocellular carcinoma patients: a multicenter retrospective study

“…In 2014, a phase II clinical study reported that apatinib monotherapy could prolong the OS of advanced HCC patients (18). Considering its potential inhibitory role in post-TACE neo-angiogenesis, a series of studies have shown clinical benefits of TACE-apatinib in unresectable HCC compared with TACE-alone (19)(20)(21)(22)(23)(24). However, no previous comparison between TACE-apatinib and TACE-sorafenib has been conducted.…”

Advanced Hepatocellular Carcinoma With Hepatic Arterioportal Shunts: Combination Treatment of Transarterial Chemoembolization With Apatinib

“…However, some previous studies reported that TACE is beneficial for patients with advanced HCC (Bai et al, 2013;Choi et al, 2013;Zhao et al, 2013). Recently, an increasing number of studies have demonstrated that a combination of TACE with apatinib treatment (TACE-apatinib) may prolong the survival of selected patients with BCLC stage-C HCC (Lu et al, 2017;Yang et al, 2019;Zhao et al, 2020). To our best knowledge, there have been few reports regarding the use of TACE-apatinib as a treatment modality in advanced HCC patients with APS.…”