Efficacy and safety of lenvatinib versus sorafenib in first-line treatment of advanced hepatocellular carcinoma: A meta-analysis

Abstract

ObjectiveLenvatinib and sorafenib are first-line oral multikinase inhibitors approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the primary therapeutic agent among these two remains controversial. This meta-analysis aimed to estimate the efficacy and safety of lenvatinib and sorafenib in patients with advanced HCC.MethodsPubMed, Cochrane Library, Web of Science, and Embase databases were searched for relevant research published up to June 30, 2022. After quality assessment and data extraction of the included studies, RevMan 5.3 software was used for analysis. Odds ratio (OR) and hazard ratio (HR) with a 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model.ResultsFifteen studies containing 3908 patients were included after final scrutiny. Our meta-analysis showed that there was no significant difference in overall survival (OS) between the lenvatinib and sorafenib groups (HR = 0.86; 95% CI: 0.72–1.02; p = 0.09); however, the progression-free survival (PFS) (HR = 0.63; 95% CI: 0.53–0.74; p < 0.00001), complete response (CR) (OR = 5.61; 95% CI: 2.71–11.64; p < 0.00001), partial response (PR) (OR = 4.62; 95% CI: 3.06–6.98; p < 0.00001), objective response rate (ORR) (OR = 5.61; 95% CI: 3.90–8.09; p < 0.00001), and disease control rate (DCR) (OR = 2.42; 95% CI: 1.79–3.28; p < 0.00001) in the lenvatinib group were significantly better than those in the sorafenib group. In terms of treatment safety, lenvatinib had similar incidences of any grade adverse events (AEs) (OR = 0.99; 95% CI: 0.47–2.09; p = 0.98) and grade ≥ 3 AEs (OR = 1.17, 95% CI; 1.00–1.37; p = 0.05) compared to sorafenib. Besides, lenvatinib was significantly associated with a higher incidence of hypertension, proteinuria, fatigue, decreased appetite, and weight loss, whereas sorafenib was associated with a higher incidence of diarrhea and hand-foot skin reaction (p < 0.05).ConclusionGiven its potential survival benefit and good tolerability, lenvatinib is an appropriate and promising alternative to sorafenib as first-line systemic therapy in patients with advanced HCC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD 42022327398.

Efficacy and safety of transarterial chemoembolization plus lenvatinib in the treatment of advanced hepatocellular carcinoma: A meta-analysis

“…[31][32][33][34] lenvatinib is a TKI that can replace sorafenib in the first-line treatment of HCC. [35] In contrast to Sorafenib, it is characterized by its strong activity against fibroblast growth factor receptors, [36] and recent studies have shown that it also has immunomodulatory activity. [37] In 2018, the REFLECT trial [38] demonstrated that lenvatinib was superior to sorafenib in improving ORR and prolonging PFS.…”

Clinical Significance of Non-Coding RNA Regulation of Programmed Cell Death in Hepatocellular Carcinoma

“…However, the current landscape has been significantly altered by the introduction of lenvatinib, a multitargeted tyrosine kinase inhibitor [ 109 , 110 ]. As a novel first-line treatment option for HCC, lenvatinib has demonstrated non-inferior overall survival, improved progression-free survival, a higher response rate, and a better disease control rate compared to sorafenib in multiple clinical trials [ 111 , 112 ].…”

Development and in functional study of a bi-specific sustained release drug-loaded nano-liposomes for hepatocellular carcinoma

“…5 Despite the excellent clinical results of LEN, it still has some adverse effects. 6,7 Some patients experienced adverse effects such as hypertension and arterial thromboembolism with LEN. 8 In phase III clinical studies of patients with HCC treated with LEN, the incidence of adverse reactions with LEN was 99% in all cases, 3 leaving only the option of reducing the frequency of dosing or changing to another drug.…”

“…12 Fe 3 O 4 nano-particles modified by polyethylene glycol (PEG) can increase the water solubility and biocompatibility of drug-loaded materials, avoid the recognition of reticuloendothelial system, prolong the circulation time of drug-loaded materials in vivo, etc. 7 Fe 3 O 4 nano-particles can be metabolized in vivo, and the material itself can be used to treat anemia, such as the “Feraheme” drug, which can be applied in vivo. 13,14 Studies have shown that when magnetic nano-materials are used as contrast agents for MRI, they can form multifunctional drug delivery and imaging systems, and take advantage of the special microenvironment of tumor tissues to design and prepare “smart” nano-drug release systems to improve the therapeutic and imaging effects at the lesion site.…”