# Systematic review of the efficacy and safety of lenvatinib vs. sorafenib as first-line treatments for hepatocellular carcinoma

## TL;DR

This study compares lenvatinib and sorafenib for treating liver cancer, finding lenvatinib more effective but with more side effects.

## Contribution

A systematic review and meta-analysis comparing lenvatinib and sorafenib as first-line treatments for hepatocellular carcinoma.

## Key findings

- Lenvatinib significantly prolongs progression-free and overall survival compared to sorafenib.
- Lenvatinib increases the risk of several toxicities, including gastrointestinal and metabolic issues.
- Lenvatinib may synergize with immunotherapy by modifying the tumor microenvironment.

## Abstract

•Lenvatinib was associated with a higher incidence of ascites and bilirubin elevation, highlighting the need for vigilant liver function monitoring.•Lenvatinib’s inhibition of VEGFR, FGFR, and PDGFR pathways contributes to its superior anti-angiogenic and anti-proliferative effects.•Preclinical evidence suggests lenvatinib may synergize with immunotherapy by modifying the tumor microenvironment, offering novel therapeutic avenues.•Economic analyses indicate lenvatinib is more cost-effective than sorafenib, supporting its adoption in resource-limited settings.

Lenvatinib was associated with a higher incidence of ascites and bilirubin elevation, highlighting the need for vigilant liver function monitoring.

Lenvatinib’s inhibition of VEGFR, FGFR, and PDGFR pathways contributes to its superior anti-angiogenic and anti-proliferative effects.

Preclinical evidence suggests lenvatinib may synergize with immunotherapy by modifying the tumor microenvironment, offering novel therapeutic avenues.

Economic analyses indicate lenvatinib is more cost-effective than sorafenib, supporting its adoption in resource-limited settings.

This study aimed to explore the efficacy and safety of lenvatinib and sorafenib as first-line treatments for hepatocellular carcinoma.

The authors searched PubMed, Web of Science, Cochrane, CNKI, Wanfang, and other databases and compared the clinical efficacy of lenvatinib and sorafenib as first-line treatments for hepatocellular carcinoma. Two participants screened the literature, collated the data, and evaluated the literature according to the inclusion and exclusion criteria. RevMan 5.4 software was used for meta-analysis of the included studies.

Ten studies were included in the meta-analysis. The results of the meta-analysis showed that, in terms of efficacy, compared with sorafenib, lenvatinib prolongs PFS in patients with hepatocellular carcinoma (HR = 85.50, 95 % CI: 38.53‒189.73, p < 0.00001) and OS (HR = 36.73, 95 % CI: 20.28–66.52, p < 0.00001), and the differences were statistically significant. In terms of safety, the risk of toxicities in the lenvatinib group at any level of gastrointestinal toxicities, metabolism/nutrition toxicities, hematological toxicities, Renal/Urinary, Vascular toxicities, and endocrine toxicities was significantly higher in the lenvatinib group than in the sorafenib group. The risks of metabolism/nutrition toxicities, renal/urinary toxicities, and vascular toxicities above grade III were significantly higher than those in the sorafenib group. The Skin/Subcutaneous Tissue toxicities of any grade and above were significantly lower than those in the sorafenib group.

As a first-line treatment for hepatocellular carcinoma, lenvatinib can prolong PFS and OS and improve the clinical benefit rate and quality of life of patients. The increased risk of specific adverse events with lenvatinib requires diligent clinical oversight.

The results demonstrate that Lenvatinib significantly prolongs both Progression-Free Survival (PFS) and Overall Survival (OS) when compared to Sorafenib. The safety profile indicates that the Lenvatinib group had a higher risk of toxicities, including nausea, diarrhea, decreased appetite, and hypertension.

Image, graphical abstract