Transarterial chemoembolization (TACE) plus tyrosine kinase inhibitors versus TACE in patients with hepatocellular carcinoma: a systematic review and meta-analysis

Abstract

Purpose Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC. Methods We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio’s random-effects model. Quality assessments were performed using the Newcastle–Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs). Results The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65–0.80), OS (combined HR 0.57, 95% CI 0.49–0.67), and objective response rate (OR 2.13, 95% CI 1.23–3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88–177.23), diarrhea (OR 18.13%, 95%CI 9.32–35.27), and hypertension (OR 12.24%, 95%CI 5.89–25.42). Conclusions Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings. Trial registration PROSPERO registration number: CRD42022298003.

Combination treatment of transcatheter arterial chemoembolization, intensity-modulated radiotherapy, and sorafenib for hepatocellular carcinoma with macrovascular invasion

“…For advanced HCC patients with MVI, TACE was found to be a safe and acceptable treatment when the patient’s hepatic function was tolerable, and collateral circulation of the portal vein had formed in the hepatic hilar region. [ 27 , 35 ] However, considering factors such as the blood supply of the tumor and the formation of collateral circulation, the complete necrosis rate of TACE alone was relatively low in these patients. Moreover, ischemia and hypoxia induced by TACE embolization might elevate the expression of HIF-1α, leading to increased VEGF expression and subsequent tumor neovascularization.…”

“…[24] Additionally, previous studies had demonstrated that the combination of sorafenib with local tumor treatments, such as TACE or EBRT, could achieve superior therapeutic effects in HCC patients with PVTT, compared to sorafenib alone. [25][26][27] A pivotal phase III clinical trial contrasted the efficacy of sorafenib monotherapy (s-m group) with sorafenib plus local treatment (including intra-arterial chemotherapy and radiation therapy, referred to as the s-lrts group) in advanced HCC patients. [28] Among the 290 patients in this trial, those in the s-lrts group experienced both a median PFS of 5.3 months and a median OS of 8.5 months, exceeding the outcomes in the s-m group.…”

Influence of transcatheter arterial embolization on symptom distress and fatigue in liver cancer patients

“…This may also contribute to a more pronounced post-treatment fatigue, as patients may experience the biological effects of the drug over an extended period. When used in conjunction with gel, it effectively inhibits the development of new tumor blood vessels, achieving therapeutic efficacy[ 23 , 24 ]. Consequently, patients with larger tumor diameters may receive higher embolization doses, leading to transient liver and gallbladder ischemia, hepatomegaly, and peritoneal stimulation-induced pain.…”

Efficacy and safety of transarterial chemoembolization combined with lenvatinib and camrelizumab in patients with BCLC-defined stage C hepatocellular carcinoma

“…( 19 ) compared TACE in combination with lenvatinib with lenvatinib monotherapy in the treatment of patients with advanced HCC, resulting in a mOS of 17.8 months in the combination group and 11.5 months in the lenvatinib monotherapy group, showing a significant advantage of TACE in combination with lenvatinib in prolonging survival. The results of a meta-analysis involving 8,246 patients showed that TACE combined with tyrosine kinase inhibitors (TKIs) benefited HCC patients in terms of OS and tumor response rate compared to TACE ( 20 ).…”