Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Cheon, Jaekyung; Chon, Hong Jae; Bang, Yeonghak; Park, Neung Hwa; Shin, Jüng Woo; Kim, Kang Mo; Lee, Han Chu; Lee, Joo-Ho; Yoo, Changhoon; Ryoo, Baek‐Yeol

doi:10.1159/000508901

Cited by 47 publications

(73 citation statements)

References 33 publications

(33 reference statements)

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“…In this study population, sorafenib (59.2%) and lenvatinib (38.8%), the agents previously approved as first-line therapy, were most frequently used as second-line therapy after failure of atezolizumab-bevacizumab. Efficacy outcomes of sorafenib and lenvatinib in this study were in line with the results of these agents in the prospective and real-world data as first-line therapy [3,11,12]. While DCR was similar between patients treated with sorafenib and lenvatinib (62.1 vs. 63.2%), all patients who achieved PR were treated with lenvatinib and ORR per RECIST v1.1 tended to be higher with lenvatinib (15.8%) compared to sorafenib (0%).…”

Section: Discussionsupporting

confidence: 83%

Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study

et al. 2021

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Introduction: Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear. Methods: This multinational, multicenter, and retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab between July 2016 and April 2019. Results: Among 71 patients treated with atezolizumab-bevacizumab, a total of 49 patients who received subsequent systemic therapy were included in this analysis; the median age was 60 years (range, 37–80) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib (n = 29), lenvatinib (n = 19), and cabozantinib (n = 1), were used as second-line therapy for all patients. The objective response rate and disease control rate were 6.1 and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.8–4.9) and 14.7 months (95% CI 8.1–21.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 vs. 2.5 months; p = 0.004), although there was no significant difference in median OS (16.6 vs. 11.2 months; p = 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome (n = 26, 53.1%), fatigue (n = 14, 28.6%), hypertension (n = 14, 28.6%), and diarrhea (n = 12, 24.5%). Conclusion: Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.

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Section: Discussionsupporting

confidence: 83%

Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study

et al. 2021

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“…Many real-world studies have reported the short-term therapeutic response of lenvatinib, resulting in an ORR of 29.9-53.5%, as assessed by mRECIST [17][18][19][20][21][22][23][24], and 14-25%, as assessed by RECIST ver.1.1 [19,22,25,26]. These findings seemed to be in agreement with the results of phase 2 and 3 studies (Table 1).…”

Section: Therapeutic Response Of Lenvatinib 21 the Ojective Responssupporting

confidence: 86%

“…The median OS was 13.6 months (95% CI 12.1-14.9) in a phase 3 study [12]. The median OS was shown to be 7.1-13.3 months, according to some retrospective studies [19,21,22,26], and modified ALBI (mALBI) grade 2b or 3 [24], Child-Pugh class B [21], BCLC advanced stage [21,35], and elevated C-reactive protein [36] were found to be significant unfavorable factors. While the starting dose of sorafenib did not influence OS according to one retrospective study [37], the patients with the higher RDI of lenvatinib (>67%) at eight weeks had significantly better OS in comparison to those with lower RDI (≤67%) [19].…”

Section: The Progression-free Survival and Overall Survivalmentioning

confidence: 98%

“…PFS was defined as the time from randomization (in phase 3 study) or start of treatment (in real-world studies) to disease progression or death. The median PFS in lenvatinibtreated patients was reported to be 7.3 months (95% confidence interval (CI) 5.6-7.5) in a phase 3 study [12], while some of the retrospective studies reported the median PFS of 4.3-9.8 months [17,18,20,22,23,25,26]. Our retrospective study reported that the BCLC intermediate stage was significantly associated with PFS in a multivariate analysis (median PFS; 8.0 months in intermediate stage, 4.0 months in advanced stage) [18].…”

Section: The Progression-free Survival and Overall Survivalmentioning

confidence: 99%

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Lenvatinib for Hepatocellular Carcinoma: A Literature Review

2021

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Lenvatinib, which is an oral multikinase inhibitor, showed non-inferiority to the sorafenib in terms of overall survival (OS) and a higher objective response rate (ORR) and better progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). A good liver function and Barcelona Clinic Liver Cancer (BCLC) intermediate stage were the key factors in achieving therapeutic efficacy. The management of adverse events plays an important role in continuing lenvatinib treatment. While sequential therapies contributed to prolonging overall survival, effective molecular targeted agents for the administration after lenvatinib have not been established. Repeated transcatheter arterial chemoembolization (TACE) was associated with a decline in the liver function and poor therapeutic response in BCLC intermediate patients. Recently, the Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed the criteria for TACE unsuitability. Upfront systemic therapy may be better for the BCLC intermediate stage HCC patients with a high tumor burden, while selective TACE will be recommended for obtaining a curative response in patients with a low tumor burden. This article reviews the therapeutic response, management of adverse events, post-progression treatment after Lenvatinib, and treatment strategy for BCLC intermediate stage HCC.

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“…Alongside these promising results, a retrospective Korean experience on 92 patients suggested a less enthusiastic picture, showing lower mPFS and mOS (4 months and 6 months, respectively) for patients with high disease burden (28 cases). 38 Even in this case, the CP B subset showed statistically lower ORR, mPFS and mOS (5.6%, 2.6 months, 5.3 months, respectively) when compared to patients with preserved liver function (CP A). 38 Finally, a retrospective analysis on 181 patients treated with first-line lenvatinib (126 classified as CP A and 55 classified as CP B) found a significant association between CP score, response rate and survival, suggesting a worse outcome when impaired liver function was present.…”

Section: Outlook: First-line Sorafenib and Lenvatinibmentioning

confidence: 59%

A Comparison of Lenvatinib versus Sorafenib in the First-Line Treatment of Unresectable Hepatocellular Carcinoma: Selection Criteria to Guide Physician’s Choice in a New Therapeutic Scenario

Dipasquale¹,

Marinello²,

Santoro³

2021

JHC

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Hepatocellular carcinoma (HCC) is the fifth most common malignancy across the world. Alongside improvement in local approaches for early stages, the prognosis of patients with advanced disease remains poor. The tyrosine kinase inhibitor sorafenib was the first drug approved for advanced HCC. During the past decade, this has been extensively explored in real-life settings, such as Eastern Cooperative Oncology Group performance status 2, Child-Pugh B liver function, chronic kidney disease, HIV infection, transplant recipients and the elderly. After 10 years, the multikinase inhibitor lenvatinib was approved in first-line setting. The Phase III REFLECT trial established the non-inferiority of lenvatinib compared with sorafenib in terms of overall survival, meanwhile exploratory analysis suggests a potential benefit over sorafenib for patients with HBV chronic infection and positive alpha-fetoprotein value. Experience with lenvatinib for patients not matching the REFLECT trial criteria remains promising but still retrospective. Indeed, the treatment sequence after lenvatinib still remains a crucial issue, considering that standard second-line options were tested only in patients who progressed to sorafenib. Overall, the choice between lenvatinib and sorafenib should take into account key selection criteria from randomized trials, evidence to date in special clinical situations, the physician’s experience and patient’s preference. Fast approval of atezolizumab plus bevacizumab as first-line treatment for advanced HCC brought an additional element in this scenario. Undoubtedly, lenvatinib and sorafenib remain available options for patients who are not suitable or those progressed to combination immunotherapy. It is conceivable that new systemic options will contribute to design a new treatment algorithm for HCC in the near future. Meanwhile, prospective studies and biomarker analysis are needed to help physicians in the choice between lenvatinib and sorafenib.

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Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Cited by 47 publications

References 33 publications

Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study

Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study

Lenvatinib for Hepatocellular Carcinoma: A Literature Review

A Comparison of Lenvatinib versus Sorafenib in the First-Line Treatment of Unresectable Hepatocellular Carcinoma: Selection Criteria to Guide Physician’s Choice in a New Therapeutic Scenario

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