Liver Cancer最新文献

[This corrects the article DOI: 10.1159/000537947.].

Introduction: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety in patient subpopulations with Vp4 portal vein tumor thrombosis (PVTT) and other high-risk prognostic factors are reported.

Methods: IMbrave150 was a global, randomized (2:1), open-label, phase 3 study in systemic treatment-naive patients with unresectable HCC; OS and PFS were co-primary endpoints. Exploratory analyses compared the efficacy and safety of atezolizumab 1,200 mg plus bevacizumab 15 mg/kg every 3 weeks versus sorafenib 400 mg twice daily in patients (i) with and without Vp4 PVTT alone and (ii) with and without high-risk prognostic factors.

Results: In patients with Vp4 PVTT, median OS was 7.6 months (95% CI: 6.0-13.9) with atezolizumab plus bevacizumab (n = 48) and 5.5 months (95% CI: 3.4-6.7) with sorafenib (n = 25; HR 0.62 [95% CI: 0.34-1.11]; descriptive p = 0.104). Median PFS in the respective arms was 5.4 months (95% CI: 3.6-6.9) and 2.8 months (95% CI: 1.5-5.3; HR 0.62 [95% CI: 0.35-1.09]; descriptive p = 0.094). In patients without Vp4, median OS was 21.1 months (95% CI: 18.0-24.6) with atezolizumab plus bevacizumab (n = 288) and 15.4 months (95% CI: 12.6-18.6) with sorafenib (n = 140; HR 0.67 [95% CI: 0.51-0.88]; descriptive p = 0.003). Median PFS in the respective arms was 7.1 months (95% CI: 6.1-9.6) and 4.7 months (95% CI: 4.2-6.1; HR 0.64 [95% CI: 0.51-0.81]; descriptive p < 0.001). The high-risk versus non-high-risk populations had similar outcome patterns. In the respective treatment arms, grade ≥3 treatment-related adverse events occurred in 43% and 48% of patients with Vp4 and 46% and 47% of patients without Vp4.

Conclusion: Regardless of VP4 PVTT or other high-risk features of unresectable HCC, which have often resulted in exclusion from other front-line trials, patients benefited from atezolizumab and bevacizumab versus sorafenib.

Introduction: Given suboptimal performance of ultrasound-based surveillance for early hepatocellular carcinoma (HCC) detection in patients with cirrhosis, there is interest in alternative surveillance strategies, including blood-based biomarkers. We aimed to evaluate the cost-effectiveness of biomarker-based surveillance in patients with cirrhosis.

Methods: We constructed a decision-analytic model to compare ultrasound/alpha-fetoprotein (AFP) and biomarker-based surveillance strategies in 1,000,000 simulated patients with compensated cirrhosis. Model inputs for adherence, benefits, and harms of each strategy were based on literature review, and costs were derived from the Medicare fee schedule. Primary outcomes were quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) of the surveillance strategies, with cost-effectiveness assessed at a threshold of USD 150,000 per QALY. We performed sensitivity analyses for HCC incidence, test performance characteristics, surveillance adherence, and biomarker costs.

Results: In the base case, both ultrasound/AFP and biomarker-based surveillance were cost-effective versus no surveillance, with ICERs of USD 105,620, and USD 101,295, per QALY, respectively. Biomarker-based surveillance was also cost-effective versus ultrasound/AFP, with an ICER of USD 14,800 per QALY. Biomarker sensitivity exceeding 80%, cost below USD 210, or adherence exceeding 58% were necessary for biomarker-based screening to be cost-effective versus ultrasound/AFP. In two-way sensitivity analyses, biomarker costs were directly related with test sensitivity and adherence, whereas sensitivity and adherence were inversely related. In a probabilistic sensitivity analysis, biomarker-based screening was the most cost-effective strategy in most (65%) simulations.

Conclusion: Biomarker-based screening appears cost-effective for HCC screening, but results are sensitive to test sensitivity, adherence, and costs.

Introduction: The combination of atezolizumab/bevacizumab has emerged as an effective first-line treatment for advanced hepatocellular carcinoma (HCC). However, this therapy is potentially associated with bleeding complications, warranting a comprehensive analysis of their incidence and severity. This meta-analysis aims to synthesize available evidence from clinical trials and observational studies to quantify the prevalence of bleeding following atezolizumab/bevacizumab administration.

Methods: This meta-analysis focused on HCC treatment using atezolizumab/bevacizumab, particularly examining bleeding complications. It determined the prevalence of bleeding post-administration and compared the risk ratio with tyrosine kinase inhibitors (sorafenib or lenvatinib). Risk factors for bleeding complications were also evaluated.

Results: From 28 studies involving 3,895 patients, the pooled prevalence of bleeding side effects was 8.42% (95% CI: 5.72-11.54). Grade III or IV bleeding occurred in 4.42% (95% CI: 2.64-6.10) of patients, with grade V bleeding observed in 2.06% (95% CI: 0.56-4.22). Gastrointestinal bleeding, predominantly variceal, was the most common, with a prevalence of 5.48% (95% CI: 3.98-7.17). Subgroup analysis indicated variability in bleeding rates based on study design and geographical location. Atezolizumab/bevacizumab treatment exhibited a 2.11 times higher prevalence of bleeding compared to tyrosine kinase inhibitors (95% CI: 1.21-3.66). Meta-regression identified high body mass index (BMI) and higher proportion of albumin-bilirubin (ALBI) grade 3 as significant risk factors for bleeding complications.

Conclusion: Atezolizumab/bevacizumab therapy for advanced HCC carries a heightened risk of gastrointestinal bleeding, exceeding that of tyrosine kinase inhibitors. High BMI and higher ALBI grade are key predictors of bleeding complications, emphasizing the need for cautious patient selection and monitoring.

[This corrects the article DOI: 10.1159/000537686.].

Recent advances in systemic therapy for hepatocellular carcinoma (HCC) have led to debates about the feasibility of combination therapies, such as systemic therapy combined with surgery or transarterial chemoembolization, for patients with advanced HCC. However, a lack of consensus on the oncological resectability criteria has hindered discussions of "conversion therapy" and the optimal management in patients with HCC. To address this issue, the Japan Liver Cancer Association (JLCA) and the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) established a working group and discussed the concept of borderline resectable HCC. Herein, we present a consensus statement from this expert panel on the resectability criteria for HCC from the oncological standpoint under the assumption of technically and liver-functionally resectable situations. The criteria for oncological resectability in HCC are classified into three grades: resectable, representing an oncological status for which surgery alone may be expected to offer clearly better survival outcomes as compared with other treatments; borderline resectable 1, representing an oncological status for which surgical intervention as a part of multidisciplinary treatment may be expected to offer survival benefit; and borderline resectable 2, representing an oncological status for which the efficacy of surgery is uncertain and the indication for surgery should be determined carefully under the standard multidisciplinary treatment. These criteria aim to provide a common language for discussing and analyzing the treatment strategies for advanced HCC. It is also expected that these criteria will be optimized, modified, and updated based on further advancements in systemic therapies and future validation studies.