Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Kuo, Yuan-Hung; Lu, Sheng–Nan; Chen, Yen‐Yang; Kee, Kwong‐Ming; Yen, Yi‐Hao; Hung, Chao‐Hung; Hu, Tsung–Hui; Chen, Chien‐Hung; Wang, Jing‐Houng

doi:10.3389/fonc.2021.737767

Cited by 20 publications

(33 citation statements)

References 25 publications

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“…Of the 24 studies included, one was a phase III randomized controlled trial (RCT) [ 8 ], and the other 23 were retrospective studies [ 8 , 9 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], involving 2438 patients with unresectable HCC who received first-line treatment with lenvatinib. The initial dose of oral lenvatinib was 12 mg QD for patients with a body weight of ≥60 kg, or 8 mg QD for those with a body weight of <60 kg.…”

Section: Resultsmentioning

confidence: 99%

Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Wang

et al. 2022

Cancers

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Lenvatinib was approved in 2018 as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). This systematic review and meta-analysis aimed to provide the most updated evidence about the efficacy and safety of lenvatinib as a first-line treatment for unresectable HCC. An electronic search of the PubMed database, Web of Science, Embase, and Cochrane Library was undertaken to identify all relevant studies up to May 2022. The pooled effect sizes were calculated based on the random-effects model. One phase III randomized controlled trial and 23 retrospective studies of 2438 patients were eligible for analysis. For patients treated with lenvatinib as first-line treatment, the pooled median overall survival (OS), median progression-free survival (PFS), 1-year OS rate, 1-year PFS rate, objective response rate (ORR), and disease control rate (DCR) were 11.36 months, 6.68 months, 56.0%, 27.0%, 36.0% and 75.0%, respectively. Lenvatinib showed a significantly superior efficacy compared with sorafenib (HR for OS, 0.85 and HR for PFS, 0.72; OR for ORR, 4.25 and OR for DCR, 2.23). The current study demonstrates that lenvatinib can provide better tumor responses and survival benefits than sorafenib as a first-line treatment for unresectable HCC, with a comparable incidence of adverse events.

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Section: Resultsmentioning

confidence: 99%

Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Wang

et al. 2022

Cancers

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“…Regarding clinical observations, in a randomized clinical trials comparing anti-cancer effectiveness it has been demonstrated that treatment of RR-DTC with lenvanitib was associated with a longer progression-free survival compared with sorafenib [ 8 , 28 ]. In case of treatment of HCC, lenvatinib showed comparable overall survival and progression-free survival but longer time to progression and better tumor response compared to sorafenib [ 29 , 30 ]. However, treatment of both, i.e., RR-DTC and HCC, with lenvatinib was associated with more frequently occurring severe adverse effects, especially hypertension and proteinuria [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…In case of treatment of HCC, lenvatinib showed comparable overall survival and progression-free survival but longer time to progression and better tumor response compared to sorafenib [ 29 , 30 ]. However, treatment of both, i.e., RR-DTC and HCC, with lenvatinib was associated with more frequently occurring severe adverse effects, especially hypertension and proteinuria [ 28 , 29 , 30 ]. It should be noted that generally adverse events lead to dose reduction or discontinuation of treatment more frequently in cases of lenvatinib than ofsorafenib [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Sorafenib versus Lenvatinib Causes Stronger Oxidative Damage to Membrane Lipids in Noncancerous Tissues of the Thyroid, Liver, and Kidney: Effective Protection by Melatonin and Indole-3-Propionic Acid

et al. 2022

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Sorafenib and lenvatinib are multi-targeted tyrosine kinase inhibitors which are currently approved to treat advanced hepatocellular carcinoma, renal cell carcinoma and radioiodine-refractory differentiated thyroid carcinoma. However this treatment is often limited due to common adverse events which may occur via oxidative stress. The study aims to compare sorafenib- and lenvatinib-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) in homogenates of porcine noncancerous tissues of the thyroid, the liver, and the kidney and to check if it can be prevented by antioxidants melatonin and indole-3-propionic acid (IPA). Homogenates of individual tissues were incubated in the presence of sorafenib or lenvatinib (1 mM, 100 µM, 10 µM, 1 µM, 100 nM, 10 nM, 1 nM, 100 pM) together with/without melatonin (5.0 mM) or IPA (5.0 mM). The concentration of malondialdehyde + 4-hydroxyalkenals, as the LPO index, was measured spectrophotometrically. The incubation of tissue homogenates with sorafenib resulted in a concentration-dependent increase in LPO (statistically significant for concentrations of 1mM and 100 µM in the thyroid and the liver, and of 1 mM, 100 µM, and 10 µM in the kidney). The incubation of thyroid homogenates with lenvatinib did not change LPO level. In case of the liver and the kidney, lenvatinib increased LPO but only in its highest concentration of 1 mM. Melatonin and IPA reduced completely (to the level of control) sorafenib- and lenvatinib-induced LPO in all examined tissues regardless of the drug concentration. In conclusion, sorafenib comparing to lenvatinib is a stronger damaging agent of membrane lipids in noncancerous tissues of the thyroid, the liver, and the kidney. The antioxidants melatonin and IPA can be considered to be used in co-treatment with sorafenib and lenvatinib to prevent their undesirable toxicity occurring via oxidative stress.

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“…Second, the cancer stage at the start of TKI therapy was lower in the lenvatinib group than in the sorafenib group. Recent real‐world clinical studies and propensity score matching analysis of aHCC comparing lenvatinib and sorafenib have shown that lenvatinib treatment is more effective 17–19 . In addition, the molecular‐targeted therapy is to start as early as possible for patients who are unsuitable for TACE, although chemotherapy has been formerly introduced only after repeated TACE 11 .…”

Section: Discussionmentioning

confidence: 99%

“…Recent real‐world clinical studies and propensity score matching analysis of aHCC comparing lenvatinib and sorafenib have shown that lenvatinib treatment is more effective. 17 , 18 , 19 In addition, the molecular‐targeted therapy is to start as early as possible for patients who are unsuitable for TACE, although chemotherapy has been formerly introduced only after repeated TACE. 11 Changes in the position of chemotherapy for HCC over time may be a limitation to the present analysis.…”

Section: Discussionmentioning

confidence: 99%

Significance of post‐progression therapy after tyrosine kinase inhibitors for advanced hepatocellular carcinoma

Yano

Yamamoto

Minami³

et al. 2022

JGH Open

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Background and Aim: Molecular-targeted therapies such as sorafenib and lenvatinib have long been used as first-line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post-progression therapy. To investigate the significance of post-progression therapy, we analyzed the outcomes of aHCC patients following first-line molecular-targeted therapy in a real-world study. Methods: This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first-line therapy between January 2011 and September 2021. Results: In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P < 0.001). Kaplan-Meier analysis revealed no significant differences in progressionfree survival and overall survival (OS) between the two treatments. Multivariate analysis revealed that fibrosis-4 index, disease control rate, post-progression therapy, and use of an immune checkpoint inhibitor (ICI) were significantly associated with OS. OS was significantly longer in patients who received post-progression therapy than in those who did not (log-rank P < 0.001). Most patients who received an ICI as post-progression therapy had previously received lenvatinib. Among lenvatinib-treated patients, OS was significantly longer in patients who received an ICI than in patients received another or no post-progression therapy (P = 0.004). Conclusion:The introduction of newer drugs for post-progression therapy is expected to prolong survival. ICI-based regimens appear to be effective after lenvatinib.

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Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Cited by 20 publications

References 25 publications

Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Sorafenib versus Lenvatinib Causes Stronger Oxidative Damage to Membrane Lipids in Noncancerous Tissues of the Thyroid, Liver, and Kidney: Effective Protection by Melatonin and Indole-3-Propionic Acid

Significance of post‐progression therapy after tyrosine kinase inhibitors for advanced hepatocellular carcinoma

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