Relative Efficacy of Systemic Treatments for Patients with Advanced Hepatocellular Carcinoma According to Viral Status: A Systematic Review and Network Meta-Analysis

Park, Jisun; Cho, Jinhyun; Lim, Joo Han; Lee, Moon Hee; Kim, Jinchul

doi:10.1007/s11523-019-00651-7

Cited by 12 publications

(11 citation statements)

References 38 publications

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“…For PFS, lenvatinib ranked first over atezolizumab plus bevacizumab. This finding supports previous meta-analyses that have shown lenvatinib to have a particularly strong anti-tumor effect vs sorafenib in patients with HBV-related HCC[ 44 , 45 ]. It is unclear why lenvatinib may have a particularly good anti-tumor effect in HBV-related HCC, but it may be due to the impact of lenvatinib on the immune microenvironment, as described above.…”

Section: Discussionsupporting

confidence: 91%

Selection of first-line systemic therapies for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials

Han

Zhi

et al. 2021

WJG

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BACKGROUND The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. AIM To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. METHODS We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. RESULTS In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR) PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HR os = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). CONCLUSION There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line sys...

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Section: Discussionsupporting

confidence: 91%

Selection of first-line systemic therapies for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials

Han

Zhi

et al. 2021

WJG

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“…Data from the SHARP and the Asia-pacific trials pooled in the analysis performed by Bruix et al [13] demonstrated that non-HCV related HCC has a worse OS (HR = 0.7, p = 0.02), while HBV infection did not achieve a significant difference in patients treated with sorafenib (HR = 1.128, p = 0.4538) compared to HBV-positive HCC patients. In a more recent meta-analysis of sorafenib and lenvatinib trials, lenvatinib was shown to be the best agent for both HBV and HCV infected patients, which presented a more favorable HR versus sorafenib treated with HCC (HR 0.83, 95% CI 0.68–1.01 and HR 0.91, 95%CI 0.66–1.25, respectively) [14].…”

Section: Clinical Predictive/prognostic Markersmentioning

confidence: 99%

Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

et al. 2019

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Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

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“…The median (IQR) time from HCC diagnosis to the start of sorafenib treatment was 4 (1-44) weeks, and the median (IQR) duration of treatment was 17 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) weeks. The main reason for sorafenib treatment discontinuation was disease progression (88%).…”

Section: Hcc Systemic Treatment Patternsmentioning

confidence: 99%

Real-World Treatment Patterns and Health-Resource Utilization in Patients with Hepatocellular Carcinoma (HCC) Following Failure of Sorafenib: A Retrospective Chart Review of 127 Patients in South Korea

Novick

Cho²,

Colman

et al. 2021

Drugs - Real World Outcomes

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Background European, US, Asian and Korean treatment guidelines all recommend sorafenib as first-line systemic therapy in patients with hepatocellular carcinoma (HCC). However, due to the emergence of several new treatments, post-sorafenib treatment patterns in real-world clinical practice are less well understood. Objective This study aimed to characterize current treatment patterns and healthcare resource utilization (HRU) in patients with HCC following the failure of first-line sorafenib in a real-world setting in Korea. Patients and methods A chart review was conducted in 127 HCC patients who received systemic therapy or best supportive care following failure of first-line systemic treatment with sorafenib (2016)(2017)(2018). Anonymized data on patient characteristics, treatment patterns, and survival were abstracted by 37 physicians in Korea. ResultsThe mean (range) age of patients was 60 (37-79) years; 63 patients had low alpha-fetoprotein (AFP < 400 ng/ mL), 64 patients had high alpha-fetoprotein (AFP ≥ 400 ng/mL). Post-sorafenib, 64 (50%) patients had systemic therapy. Regorafenib, used by 54 (84%) patients in second-line, and nivolumab monotherapy, by ten (56%) patients in third-line, were the most common therapies. Hepatologist visits and hospitalizations, at an average rate of 6.89 (95% CI 6.37-7.45) and 2.24 (95% CI 1.95-2.57) per patient-year, respectively, were the key contributors of HRU. The median overall survival (95% CI) from discontinuation of sorafenib was 13.0 (9.8-20.7), 6.5 (5.0-9.5) and 9.5 (6.7-12.3) months in the low AFP, high AFP and overall group, respectively. Conclusion This real-world evidence research on treatment patterns reflected current clinical guidelines and highlighted fast progressing nature and continuing high mortality in HCC, especially among the high AFP group, underlying a need for new treatments that can lengthen survival. Results from this real-world chart review, together with existing clinical trial data, can inform future evaluations of new HCC treatments that estimate their health economic impact in Korea.

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Relative Efficacy of Systemic Treatments for Patients with Advanced Hepatocellular Carcinoma According to Viral Status: A Systematic Review and Network Meta-Analysis

Cited by 12 publications

References 38 publications

Selection of first-line systemic therapies for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials

Selection of first-line systemic therapies for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials

Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Real-World Treatment Patterns and Health-Resource Utilization in Patients with Hepatocellular Carcinoma (HCC) Following Failure of Sorafenib: A Retrospective Chart Review of 127 Patients in South Korea

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