Real-World Use of Immunotherapy for Hepatocellular Carcinoma DOI Creative Commons

Amir Sara,

Samantha M. Ruff, Anne M. Noonan

и другие.

Pragmatic and Observational Research, Год журнала: 2023, Номер Volume 14, С. 63 - 74

Опубликована: Авг. 1, 2023

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide and accounts for 90% all primary liver cancers. Chronic inflammation hallmark across prevalent etiologies among which HBV leading (33%), followed by alcohol (30%), HCV (21%), other factors like non-alcoholic steatohepatitis linked to insulin resistance/metabolic syndrome, obesity associated (16%). Deregulation tightly controlled immunological network leads disease, including chronic infection, autoimmunity, tumor development. While drives oncogenesis in liver, HCC also recruits ICOS+ FOXP3+ Tregs MDSCs upregulates immune checkpoints induce a state immunosuppression microenvironment. As such, research focused on targeting modulating system treat HCC. The Checkmate 040 Keynote 224 studies established role immunotherapy treatment patients with In Phase I II trials, nivolumab pembrolizumab demonstrated durable response rates 15-20% were subsequently approved as second-line agents after sorafenib. Due success IMbrave 150 HIMALAYA examined combination atezolizumab/bevacizumab tremelimumab/durvalumab, respectively, FDA these regimens first-time options advanced encouraging results management has led researchers evaluate if locoregional therapies may result synergistic effect. Real-world represent an invaluable tool assess verify applicability clinical trials bedside setting more varied patient population. We herein review current real-life use ICIs highlight some ongoing that are expected change recommended first-line near future.

Язык: Английский

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update DOI
John D. Gordan, Erin B. Kennedy, Ghassan K. Abou‐Alfa

и другие.

Journal of Clinical Oncology, Год журнала: 2024, Номер 42(15), С. 1830 - 1850

Опубликована: Март 19, 2024

To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC).

Язык: Английский

Процитировано

79
Phenotypes of Metabolic Dysfunction–Associated Steatotic Liver Disease–Associated Hepatocellular Carcinoma DOI
Jesús Rivera‐Esteban, Sergio Muñoz, Mónica Higuera

и другие.

Clinical Gastroenterology and Hepatology, Год журнала: 2024, Номер 22(9), С. 1774 - 1789.e8

Опубликована: Апрель 10, 2024

Язык: Английский

Процитировано

10
The current status and future of targeted-immune combination for hepatocellular carcinoma DOI Creative Commons

Liyuan Hao,

Shenghao Li,

Fanghang Ye

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 5, 2024

Hepatocellular carcinoma (HCC) is one of the most common cancers and third leading cause death worldwide. surgery, transarterial chemoembolization (TACE), systemic therapy, local ablation radiotherapy, targeted drug therapy with agents such as sorafenib. However, tumor microenvironment liver cancer has a strong immunosuppressive effect. Therefore, new treatments for are still necessary. Immune checkpoint molecules, programmed death-1 (PD-1), death-ligand 1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), along high levels cytokines, induce cell inhibition key mechanisms immune escape in HCC. Recently, immunotherapy based on inhibitors (ICIs) monotherapy or combination tyrosine kinase inhibitors, anti-angiogenesis drugs, chemotherapy agents, topical therapies offered great promise treatment cancer. In this review, we discuss latest advances ICIs combined drugs (targeted-immune combination) other targeted-immune regimens patients advanced HCC (aHCC) unresectable (uHCC), provide an outlook future prospects. The literature reviewed spans last five years includes studies identified using keywords "hepatocellular carcinoma," "immune inhibitors," "targeted therapy," "combination "immunotherapy".

Язык: Английский

Процитировано

9
Role of hepatotropic viruses in promoting hepatocellular carcinoma—current knowledge and recent advances DOI

Piotr Starnawski,

Klaudia Nowak,

Zuzanna Augustyn

и другие.

Medical Oncology, Год журнала: 2025, Номер 42(4)

Опубликована: Март 17, 2025

Язык: Английский

Процитировано

1
Soluble Urokinase Plasminogen Activator Receptor Predicts Survival and Hepatic Decompensation in Advanced Hepatocellular Carcinoma DOI Creative Commons
Fabian Jost‐Brinkmann,

Sven Lamatsch,

Minh D. Phan

и другие.

Liver International, Год журнала: 2025, Номер 45(6)

Опубликована: Май 2, 2025

ABSTRACT Background and Aims The introduction of immune checkpoint inhibitor (ICI) based therapies has significantly improved the prognosis patients with unresectable hepatocellular carcinoma (HCC). However, variable treatment response uncertain benefit in advanced liver cirrhosis emphasise urgent need for prognostic predictive biomarkers guiding patient selection. soluble urokinase plasminogen activator receptor (suPAR) is strongly associated inflammation, various types cancer. In this study, we investigated suPAR as a potential novel biomarker HCC. Methods This multicenter retrospective conducted at three German tertiary care centers, included 90 HCC measurements prior to during atezolizumab/bevacizumab therapy. Patients without ( n = 235) non‐cirrhotic other gastrointestinal tumours 155) were selected control cohorts. Results Median levels higher compared cancer patients. A strong association parameters function, but not characteristics, was observed. receiving atezolizumab/bevacizumab, most accurate independent predictor hepatic decompensation overall survival (OS). addition, able stratify risk within different Child‐Pugh classes. Conclusions SuPAR represents promising treated ICI‐based bears guide selection antitumoral systemic cirrhosis.

Язык: Английский

Процитировано

1
Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma DOI Creative Commons
Samantha M. Ruff, Ashish Manne, Jordan M. Cloyd

и другие.

Current Oncology, Год журнала: 2023, Номер 30(6), С. 5863 - 5875

Опубликована: Июнь 18, 2023

The liver maintains a balance between immune tolerance and activation in its role as filtration system. Chronic inflammation disrupts this microenvironment, thereby allowing for the rise progression of cancer. Hepatocellular carcinoma (HCC) is tumor generally diagnosed setting chronic disease. When early, primary treatment surgical resection, transplantation, or directed therapies. Unfortunately, patients with HCC often present at an advanced stage poor function, limiting options. To further complicate matters, most systemic therapies are relatively limited ineffective among Recently, IMbrave150 trial demonstrated that combination atezolizumab bevacizumab was associated better survival compared to sorafenib HCC. As such, now recommended first-line therapy these patients. Tumor cells work create immunotolerant environment by preventing stimulatory immunoreceptors upregulating expression proteins bind inhibitory immunoreceptors. ICIs block interactions bolster anti-tumor function We herein provide overview use

Язык: Английский

Процитировано

14
Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together? DOI Creative Commons

Wiebke Werner,

Maria Kuzminskaya,

Isabella Lurje

и другие.

Seminars in Liver Disease, Год журнала: 2024, Номер 44(02), С. 159 - 179

Опубликована: Май 1, 2024

Primary liver cancer, represented mainly by hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA), is one of the most common deadliest tumors worldwide. While surgical resection or transplantation are best option in early disease stages, these often present advanced stages systemic treatment required to improve survival time. The emergence immune checkpoint inhibitor (ICI) therapy has had a positive impact especially on cancers, thereby establishing immunotherapy as part first-line HCC CCA. Nevertheless, low response rates reflect usually cold immunosuppressed tumor microenvironment primary cancer. In this review, we aim summarize mechanisms resistance leading escape with special focus composition both CCA, also reflecting recent important developments ICI combination therapy. Furthermore, discuss how ICIs established cancer treatments (e.g. multikinase inhibitors chemotherapy) well more complex combinations state-of-the-art therapeutic concepts may reshape microenvironment, higher long-lasting antitumor immunity for patients.

Язык: Английский

Процитировано

6
Predicting Outcomes of Atezolizumab and Bevacizumab Treatment in Patients with Hepatocellular Carcinoma DOI Open Access
Ji Won Han, Jeong Won Jang

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11799 - 11799

Опубликована: Июль 22, 2023

A combination of atezolizumab with bevacizumab (AB) is the first regimen that has shown superiority compared to sorafenib and now being used as systemic treatment choice for hepatocellular carcinoma (HCC) patients Barcelona Liver Cancer Clinic stage C. However, a considerable number do not achieve survival or significant responses, indicating need identify predictive biomarkers initial on-treatment decisions in HCC receiving AB. In this manuscript, we summarized current data from both experimental clinical studies. This review will be beneficial clinicians researchers practice well those designing experimental, translational,

Язык: Английский

Процитировано

12
Risk of Bleeding in Hepatocellular Carcinoma Patients Treated with Atezolizumab/Bevacizumab: A Systematic Review and Meta-Analysis DOI Creative Commons

Young‐Gi Song,

Kyeong-Min Yeom,

Eun Ae Jung

и другие.

Liver Cancer, Год журнала: 2024, Номер unknown, С. 1 - 11

Опубликована: Май 22, 2024

<b><i>Introduction:</i></b> 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 their incidence and severity. This meta-analysis aims to synthesize available evidence from clinical trials observational studies quantify the prevalence following administration. <b><i>Methods:</i></b> focused on HCC using atezolizumab/bevacizumab, particularly examining complications. It determined post-administration compared risk ratio tyrosine kinase inhibitors (sorafenib or lenvatinib). Risk factors complications were also evaluated. <b><i>Results:</i></b> From 28 involving 3,895 patients, pooled side effects was 8.42% (95% CI: 5.72–11.54). Grade III IV occurred in 4.42% 2.64–6.10) grade V observed 2.06% 0.56–4.22). Gastrointestinal bleeding, predominantly variceal, most common, 5.48% 3.98–7.17). Subgroup indicated variability rates based study design geographical location. Atezolizumab/bevacizumab exhibited 2.11 times higher 1.21–3.66). Meta-regression identified high body mass index (BMI) proportion albumin-bilirubin (ALBI) 3 significant <b><i>Conclusion:</i></b> carries heightened gastrointestinal exceeding that inhibitors. High BMI ALBI are key predictors emphasizing need cautious patient selection monitoring.

Язык: Английский

Процитировано

5
CRAFITY score as a predictive marker for refractoriness to atezolizumab plus bevacizumab therapy in hepatocellular carcinoma: a multicenter retrospective study DOI Creative Commons
Masayuki Ueno,

Haruhiko Takeda,

Atsushi Takai

и другие.

Journal of Gastroenterology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 18, 2024

Abstract Background Although atezolizumab plus bevacizumab (Atezo/Bev) therapy has been used as the preferred first-line treatment for advanced hepatocellular carcinoma (HCC), up to 26% of patients do not achieve disease control, suggesting alternative treatments might be more beneficial such patients. We investigated key predictors refractoriness Atezo/Bev therapy, particularly in setting. Methods retrospectively analyzed 302 with HCC who received between October 2020 and September 2022 across nine hospitals Japan. Refractoriness was defined best overall response (BOR) progressive or stable a progression-free survival (PFS) < 180 days (RECIST v1.1). Clinical benefit BOR partial/complete PFS ≥ days. Baseline characteristics potential predictors, identified through literature review, were compared these groups. Stratifications (OS), also assessed. Results observed 126 (41.7%) patients, while 154 (51.0%) achieved clinical benefit. Due significant association line refractory rate, subsequent analysis focused on cohort ( n = 214; 72 [33.6%] showed refractoriness). Among 13 CRP AFP immunotherapy (CRAFITY) score had predictive performance, rates 24.6%, 44.6%, 57.9% CRAFITY-0, 1, 2 respectively p 0.001). OS well-stratified by this scoring system. Conclusions Approximately one-third therapy. The CRAFITY demonstrated superior performance predicting refractoriness.

Язык: Английский

Процитировано

5