Comparative Efficacy of Atezolizumab plus Bevacizumab and Other Treatment Options for Patients with Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis
Open Access
- 6 May 2021
- journal article
- research article
- Published by S. Karger AG in Liver Cancer
- Vol. 10 (3), 240-248
- https://doi.org/10.1159/000515302
Abstract
Background: Most phase 3 clinical trials of systemic therapy for first-line unresectable hepatocellular carcinoma (HCC) have failed, with the exception of SHARP, REFLECT, and IMbrave150. We conducted indirect comparisons of therapies evaluated for first-line HCC treatment. Summary: We conducted a systematic review and meta-analysis of treatments for adults with locally advanced or metastatic unresectable HCC and no prior systemic treatment, including atezolizumab plus bevacizumab, sorafenib, lenvatinib, nivolumab, selective internal radiotherapy (SIRT), transarterial chemoembolization, and placebo or best supportive care. Randomized controlled trials published from January 1, 2007, to March 12, 2020, were retrieved from MEDLINE and Embase. Qualitative assessment of heterogeneity evaluated study designs, populations, and outcomes. Indirect comparisons used generalized linear models with random effects within a Bayesian framework and informative priors. We calculated relative efficacy estimates with 95% credible intervals (CrIs) and Bayesian posterior probability estimates of atezolizumab-bevacizumab being superior to other treatments. Nine clinical studies with a total of 3,897 participants were identified from 8,783 records and used to build the all-trials evidence network. Indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus lenvatinib (odds ratio, 0.63 [95% CrI 0.39–1.04]; with 97% Bayesian posterior probability of being superior), nivolumab (0.68 [95% CrI 0.41–1.14]; 94%), sorafenib (0.59 [95% CrI 0.39–0.87]; 99%), SIRT (0.51 [95% CrI 0.32–0.82]; 100%), or placebo/best supportive care (0.40 [95% CrI 0.25–0.64]; 100%). Key Messages: Within the context of indirect comparisons, analyses of OS favored atezolizumab-bevacizumab versus other treatment options for patients with locally advanced or metastatic unresectable HCC.Keywords
This publication has 20 references indexed in Scilit:
- The Adverse Effects of Sorafenib in Patients with Advanced CancersBasic & Clinical Pharmacology & Toxicology, 2015
- Predictive distributions for between‐study heterogeneity and simple methods for their application in Bayesian meta‐analysisStatistics in Medicine, 2014
- Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinomaLiver International, 2014
- Randomized Comparison of Selective Internal Radiotherapy (SIRT) Versus Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) for the Treatment of Hepatocellular CarcinomaCardioVascular and Interventional Radiology, 2014
- Sunitinib Versus Sorafenib in Advanced Hepatocellular Cancer: Results of a Randomized Phase III TrialJournal of Clinical Oncology, 2013
- How does the DerSimonian and Laird procedure for random effects meta-analysis compare with its more efficient but harder to compute counterparts?Journal of Statistical Planning and Inference, 2010
- Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trialThe Lancet Oncology, 2008
- Sorafenib in Advanced Hepatocellular CarcinomaThe New England Journal of Medicine, 2008
- Phase II Trial Evaluating the Clinical and Biologic Effects of Bevacizumab in Unresectable Hepatocellular CarcinomaJournal of Clinical Oncology, 2008
- Statistics notes: Bayesians and frequentistsBMJ, 1998