Dataset Information

Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials.

ABSTRACT:

Background & aims

Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic treatments for hepatocellular carcinoma in terms of overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate, and incidence of adverse events (AEs).

Methods

After performing a literature review from January 2008 to September 2022, we screened 6,329 studies and reviewed 3,009 studies, leading to identification of 15 phase III trials for analysis. We extracted odds ratios for objective response rate and disease control rate, relative risks for AEs, and hazard ratios (HRs) with 95% CIs for OS and PFS, and used a frequentist network metanalysis, with fixed-effect multivariable meta-regression models to estimate the indirect pooled HRs, odds ratios, relative risks, and corresponding 95% CIs, considering sorafenib as reference.

Results

Of 10,820 included patients, 10,444 received active treatment and 376 placebo. Sintilimab + IBI350, camrelizumab + rivoceranib, and atezolizumab + bevacizumab provided the greatest reduction in the risk of death compared with sorafenib, with HRs of 0.57 (95% CI 0.43-0.75), 0.62 (95% CI 0.49-0.79), and 0.66 (95% CI 0.52-0.84), respectively. Considering PFS, camrelizumab + rivoceranib and pembrolizumab + lenvatinib were associated with the greatest reduction in the risk of PFS events compared with sorafenib, with HRs of 0.52 (95% CI 0.41-0.65) and 0.52 (95% CI 0.35-0.77), respectively. Immune checkpoint inhibitor (ICI) monotherapies carried the lowest risk for all-grade and grade ≥3 AEs.

Conclusions

The combinations of ICI + anti-vascular endothelial growth factor, and double ICIs lead to the greatest OS benefit compared with sorafenib, whereas ICI + kinase inhibitor regimens are associated with greater PFS benefit at the cost of higher toxicity rates.

Impact and implications

In the last few years, many different therapies have been studied for patients with primary liver cancer that cannot be treated with surgery. In these cases, anticancer drugs (alone or in combination) are given with the intent to keep the cancer at bay and, ultimately, to prolong survival. Among all the therapies that have been investigated, the combination of immunotherapy (drugs that boost the immune system against the cancer) and anti-angiogenic agents (drugs that act on tumoural vessels) has appeared the best to improve survival. Similarly, the combination of two types of immunotherapies that activate the immune system at different levels has also shown positive results.

Systematic review registration

PROSPERO CRD42022366330.

SUBMITTER: Fulgenzi CAM

PROVIDER: S-EPMC10070142 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials.

Fulgenzi Claudia Angela Maria CAM Scheiner Bernhard B Korolewicz James J Stikas Charalampos-Vlasios CV Gennari Alessandra A Vincenzi Bruno B Openshaw Mark R MR Silletta Marianna M Pinter Matthias M Cortellini Alessio A Scotti Lorenza L D'Alessio Antonio A Pinato David J DJ

JHEP reports : innovation in hepatology 20230218 5

<h4>Background & aims</h4>Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic treatments for hepatocellular carcinoma in terms of overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate, and incidence of adverse events (AEs).<h4>Methods</h4>After performing a literature review from January 2008 to September 2022, ...[more]

PMID: 37025943

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Dataset Information

Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials.

Background & aims

Methods

Results

Conclusions

Impact and implications

Systematic review registration

Publications

Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials.

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