RESUMO
Background: In 2020, atezolizumab-bevacizumab became the new standard of care (SOC) for first-line unresectable hepatocellular carcinoma (HCC) patients, following a decade where sorafenib was the preferred first-line treatment. In the last few years, a number of novel systemic treatments with non-inferiority and superiority to sorafenib have been approved as first-line treatments. Objectives: The objective of this systematic literature review (SLR) and network meta-analysis (NMA) was to compare randomised controlled trial evidence for atezolizumab-bevacizumab with globally relevant pharmacological comparators for first-line treatment of patients with unresectable HCC. Methods: Randomised controlled trials investigating first-line treatment of HCC in adults with no prior systemic treatment were eligible for inclusion into the SLR and were retrieved from Embase, MEDLINE, and Evidence-Based Medicine (EBM) Reviews. Interventions of interest for the NMA included atezolizumab-bevacizumab, sorafenib, lenvatinib, durvalumab (including in combination with tremelimumab), cabozantinib (including in combination with atezolizumab), camrelizumab (including in combination with rivoceranib), pembrolizumab (including in combination with lenvatinib), and tislelizumab. Random effects NMA was conducted for survival endpoints within a Bayesian framework with an informative prior distribution for between-study heterogeneity. The hazard ratios for relative treatment effect were estimated with 95% credible intervals (CrIs). Results: The SLR identified 49 studies, of which eight formed a connected evidence network permitting the indirect treatment comparison of atezolizumab-bevacizumab with comparators of interest. The indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus most comparators. All indirect treatment comparison results for atezolizumab-bevacizumab included the null value within the 95% CrI (n = 1) for OS and progression-free survival (PFS). Conclusions: The results of the NMA indicate atezolizumab-bevacizumab is associated with superior or comparable OS and PFS together with a manageable safety profile compared with globally relevant comparators in the unresected HCC indication. The findings support that atezolizumab-bevacizumab remains SOC for the management of first-line unresectable HCC patients.
RESUMO
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 atezolizu-mab 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.
RESUMO
Digital thermal monitoring (DTM) of vascular function has already been shown to correlate well with coronary artery calcium (CAC) score and coronary artery disease. To determine its utility in the metabolic syndrome (MS) and diabetes mellitus (DM), 233 asymptomatic patients with DM/MS but without coronary artery disease underwent DTM during and after 5 minutes of supra-systolic arm cuff inflation, as well as CAC. Post-cuff deflation adjusted temperature rebound (aTR) was lower in MS and DM compared with the normal group. The odds ratio of lowest vs upper 2 tertiles of aTR was 2.3 for MS and 3.5 for DM compared with the normal group, independent of age, sex, and risk factors. The area under the receiver operating characteristic curve to predict CAC > or =100 was 0.69 for metabolic status (DM/MS), 0.79 for aTR, and 0.87 for both. This study demonstrates that vascular dysfunction measured by DTM is associated with DM/MS and could potentially be used to detect asymptomatic individuals with increased subclinical atherosclerosis.
