Effectiveness of lenvatinib versus sorafenib as first- or second-line therapy in hepatocellular carcinoma: insights from real-life data, systematic review, and meta-analysis
Abstract
Background: Clinical trials showed a non-inferior efficacy of lenvatinib versus sorafenib as first- or second-line treatment for advanced hepatocellular carcinoma (HCC). However, comparative effectiveness has not been definitively established. Our study aimed to compare the effectiveness of lenvatinib versus sorafenib as first-line therapy for advanced HCC in a real-world cohort and to integrate these findings with the available current evidence on the use of both drugs as first- or second-line therapy.
Methods: We conducted a propensity score-matched analysis including patients who were treated with lenvatinib or sorafenib as first-line therapy between January 2020 and December 2024. We also performed a systematic review and meta-analysis comparing the effectiveness of lenvatinib versus sorafenib as first-line therapy and a systematic review investigating the effectiveness of tyrosine-kinase inhibitor (TKI) as second-line therapy for advanced HCC.
Results: In our matched cohort (n = 84 patients), the patients treated with lenvatinib showed longer median overall survival than those treated with sorafenib (17.7 vs 11.2 months; P = 0.224). A meta-analysis of lenvatinib versus sorafenib as first-line therapy (n = 3,549 patients) demonstrated better outcomes for lenvatinib than for sorafenib in terms of overall survival, objective response rate, and disease control rate. In a proportional meta-analysis, lenvatinib showed a significantly higher objective response rate (38% vs 9%; P < 0.001) and a higher partial response rate (36% vs 9%; P < 0.001) than sorafenib. Results from the systematic review for TKI as second-line strategy (n = 1,011 patients) showed a trend toward better outcomes with lenvatinib, although limited data are available.
Conclusions: In the first-line setting, patients treated with lenvatinib had better clinical responses than did those treated with sorafenib. For second-line treatment, evidence is limited; however, available data show a trend toward better outcomes with lenvatinib and prospective studies are needed to confirm these findings.
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BibTeX
@article{villani2026effectiveness,
title = {{Effectiveness of lenvatinib versus sorafenib as first- or second-line therapy in hepatocellular carcinoma: insights from real-life data, systematic review, and meta-analysis}},
author = {Rosanna Villani and Elisabetta Cornacchia and Nicolò Maria Sguera and Tommaso Colangelo and Tommaso Cassano and Danilo Di Bona and Gaetano Serviddio},
journal = {Gastroenterology Report},
year = {2026},
month = oct,
doi = {10.1093/gastro/goag109},
url = {https://doi.org/10.1093/gastro/goag109},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Effectiveness of lenvatinib versus sorafenib as first- or second-line therapy in hepatocellular carcinoma: insights from real-life data, systematic review, and meta-analysis
AU - Rosanna Villani
AU - Elisabetta Cornacchia
AU - Nicolò Maria Sguera
AU - Tommaso Colangelo
AU - Tommaso Cassano
AU - Danilo Di Bona
AU - Gaetano Serviddio
PY - 2026
DA - 2026/10/27
JO - Gastroenterology Report
DO - 10.1093/gastro/goag109
UR - https://doi.org/10.1093/gastro/goag109
AB - Background: Clinical trials showed a non-inferior efficacy of lenvatinib versus sorafenib as first- or second-line treatment for advanced hepatocellular carcinoma (HCC). However, comparative effectiveness has not been definitively established. Our study aimed to compare the effectiveness of lenvatinib versus sorafenib as first-line therapy for advanced HCC in a real-world cohort and to integrate these findings with the available current evidence on the use of both drugs as first- or second-line therapy. Methods: We conducted a propensity score-matched analysis including patients who were treated with lenvatinib or sorafenib as first-line therapy between January 2020 and December 2024. We also performed a systematic review and meta-analysis comparing the effectiveness of lenvatinib versus sorafenib as first-line therapy and a systematic review investigating the effectiveness of tyrosine-kinase inhibitor (TKI) as second-line therapy for advanced HCC. Results: In our matched cohort (n = 84 patients), the patients treated with lenvatinib showed longer median overall survival than those treated with sorafenib (17.7 vs 11.2 months; P = 0.224). A meta-analysis of lenvatinib versus sorafenib as first-line therapy (n = 3,549 patients) demonstrated better outcomes for lenvatinib than for sorafenib in terms of overall survival, objective response rate, and disease control rate. In a proportional meta-analysis, lenvatinib showed a significantly higher objective response rate (38% vs 9%; P < 0.001) and a higher partial response rate (36% vs 9%; P < 0.001) than sorafenib. Results from the systematic review for TKI as second-line strategy (n = 1,011 patients) showed a trend toward better outcomes with lenvatinib, although limited data are available. Conclusions: In the first-line setting, patients treated with lenvatinib had better clinical responses than did those treated with sorafenib. For second-line treatment, evidence is limited; however, available data show a trend toward better outcomes with lenvatinib and prospective studies are needed to confirm these findings.
SN - 2052-0034
ER -