Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study

Kim, Seung Up; Cheon, Jaekyung; Kim, Hye-Yeong; Kang, Beodeul; Ha, Yeonjung; Kim, D. Y.; Hwang, Seong-Gyu; Chon, Young Eun; Chon, Hong Jae

doi:10.3390/cancers14071747

Cited by 51 publications

(82 citation statements)

References 23 publications

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“…Considering these points, it is reasonable to conclude that ATEZO/BEVA has a better prognosis than LEN. Moreover, the median observation period of ATEZO/BEVA treatment was longer than in previous studies [ 6 , 7 , 17 ], which we consider a more meaningful result. Additionally, a previous report clarified that the combination of ATEZO/BEVA is superior to LEN based on a matching-adjusted indirect comparison (MAIC) using data on LEN from patients outside of randomized trials, as well as data on the ATEZO/BEVA results derived from the IMbrave150 trial [ 18 ].…”

Section: Discussionmentioning

confidence: 66%

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Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

et al. 2022

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Background A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. Objective This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. Patients and Methods This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA ( n = 186) or LEN ( n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. Results After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). Conclusions ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-022-00921-x.

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Section: Discussionmentioning

confidence: 66%

“…No clinical trial has directly compared the therapeutic effects and safety between ATEZO/BEVA and LEN. Recently, although some retrospective analyses have compared ATEZO/BEVA and LEN for HCC patients [ 6 , 7 ], the efficacy and safety of ATEZO/BEVA and LEN remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

et al. 2022

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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%

“…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. Of the 23 studies that assessed the tumor response, nineteen studies [ 9 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 27 , 28 , 31 , 32 , 33 , 34 , 35 ] applied the mRECIST, one [ 32 ] applied the RECIST 1.1, one [ 21 ] applied the RECIST 1.1 and mRECIST, and two [ 26 , 30 ] were unknown. Details of all studies and the characteristics of the patients are presented in Table 1 .…”

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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“…As such, atezo + bev is now approved for firstline therapy for unresectable HCC [95] . However, a subgroup analysis of patients from IMBrave150 revealed the ORR for patients with NASH-related HCC was 27% versus 35% among patients with HCC due to other etiologies [97] . In addition, a phase III clinical trial evaluating the efficacy and safety of lenvatinib versus atezo + bev as first-line therapy for the treatment of unresectable HCC was conducted on 232 patients in Korea.…”

Section: Impact On Therapymentioning

confidence: 98%

Alteration in immune function in patients with fatty liver disease

Gregory¹,

Perati²,

Brown³

2022

Hepatoma Res

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Nonalcoholic fatty liver disease (NAFLD) is a disease spectrum that spans simple steatosis, fibrosis, and ultimately cirrhosis, and is a leading cause of chronic liver disease globally. The severe variant of NAFLD, non-alcoholic steatohepatitis (NASH), is characterized by triglyceride accumulation within hepatocytes and the subsequent inflammatory pathway activation, ultimately progressing to cirrhosis in 10%-20% of patients. NASH is a known major risk factor for the development of hepatocellular carcinoma (HCC), and there is emerging data demonstrating the impact of NASH on immune subsets and the tumor microenvironment that may influence therapeutic response. This review describes the various ways in which the immune system is altered in patients with NASH. The innate immune system in NASH shows alterations in dendritic and Kupffer cells, impaired cytotoxicity of Natural Killer cells, and an accumulation of neutrophils. Additionally, there is emerging evidence emphasizing the role of the adaptive immune system in the development and progression of NASH, seen in the alteration of B-cells, T-cells, and NKT Cells. Due to the complex interplay of the immune system in NAFLD/NASH and its progression to HCC, many current treatments focus on targeting immune cells for HCC therapy. Recently, immune checkpoint inhibitors such as atezolizumab and bevacizumab have been approved as first-line therapy for unresectable HCC. Although an emerging field of research, further studies and clinical trials are needed to understand the complex interface of NASH, HCC and the immune response.

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Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study

Cited by 51 publications

References 23 publications

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

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

Alteration in immune function in patients with fatty liver disease

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