Real-World Effectiveness of Sorafenib versus Lenvatinib Combined with PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma.

Content Provider	Europe PMC
Author	Chiang, Hsueh-Chien Lee, Yang-Cheng Chang, Ting-Tsung Lin, Yih-Jyh Wu, Hung-Tsung Wang, Chung-Teng Chen, Chiung-Yu Chen, Po-Jun Hsieh, Ming-Tsung Lin, Sheng-Hsiang Chen, Shang-Hung Chuang, Chiao-Hsiung Wu, I-Chin Hong, Tzu-Chun Wu, Juei-Seng Han, Meng-Zhi Chen, Wei-Ting Chiang, Chien-Ming Hung, Kuan-Kai Kuo, Hsin-Yu
Editor	Tiribelli, Claudio
Copyright Year	2023
Abstract	Simple SummaryImmunotherapy using immune checkpoint inhibitors (ICIs) (e.g., programmed cell death protein-1 (PD-1) inhibitors) combined with molecular targeted agents has been evaluated in clinical trials and has shown potential synergic effects and superior efficacy in unresectable hepatocellular carcinoma (uHCC). The optimal regimen for uHCC of combination therapy with a PD-1 inhibitor plus an MTKI remains controversial. A head-to-head comparison is still lacking regarding combination strategies involving the administration of PD-1 inhibitors with different MTKIs in uHCC. This highly original study evaluates the efficacy and safety of PD-1 inhibitors in combination with sorafenib or lenvatinib in a cohort of patients with uHCC. We observed that PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Our data on efficacy and tolerability may enable clinicians to select optimal treatment strategies for HCC therapy.AbstractImmune checkpoint inhibitors (ICIs) combined with multitarget tyrosine kinase inhibitors (MTKIs) exert a synergistic effect and are effective in unresectable hepatocellular carcinoma (uHCC). However, precise data regarding the real-world clinical applications of these combination therapies in uHCC are lacking. This study compared the treatment efficacy of sorafenib versus lenvatinib in combination with programmed cell death protein-1 (PD-1) inhibitors in patients with uHCC in a clinical setting. Among 208 patients with uHCC treated with PD-1 inhibitors, 88 were administered with ICIs in combination with sorafenib or lenvatinib. The treatment response and survival outcomes were evaluated. Predictors of survival were assessed by multivariate analysis. A total of 49 patients were treated with PD-1 inhibitors combined with sorafenib, and 39 patients were treated with PD-1 inhibitors combined with lenvatinib. The lenvatinib group exhibited a stronger objective response rate (ORR) (20.51% vs. 16.33%) and had a higher disease control rate (41.03% vs. 28.57%) than did the sorafenib group. The median overall survival was longer in the lenvatinib group than the sorafenib group (13.1 vs. 7.8 months; hazard ratio = 0.39, p = 0.017). The incidence of treatment-related adverse events was similar. PD-1 inhibitors combined with lenvatinib can be a feasible treatment strategy for HCC patients receiving MTKI-based combination therapy. PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Additional larger-scale and prospective studies should be conducted to verify the study results.
Journal	Cancers
Volume Number	15
PubMed Central reference number	PMC9913272
Issue Number	3
PubMed reference number	36765812
e-ISSN	20726694
DOI	10.3390/cancers15030854
Language	English
Publisher	MDPI
Publisher Date	2023-01-30
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	immune checkpoint inhibitor sorafenib lenvatinib hepatocellular carcinoma
Content Type	Text
Resource Type	Article
Subject	Oncology Cancer Research