The Growing Skyline of Advanced Hepatocellular Carcinoma Treatment: A Review

Schipilliti, Francesca Matilde; Garajová, Ingrid; Rovesti, Giulia; Balsano, Rita; Piacentini, Federico; Dominici, Massimo; Gelsomino, Fabio

doi:10.3390/ph14010043

Cited by 9 publications

(7 citation statements)

References 113 publications

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“…HCC at early stage can often be curatively treated by effective options such as surgical resection, liver transplantation, and local ablation, which could lead to better survival outcome (2). On the contrary, advanced-stage HCC frequently presents with poor prognosis because of limited potential treatment modalities offered (3). Despite the improvement of HCC diagnostic measures and screening systems, many patients are still diagnosed at an advanced stage where systemic therapy is the main recommended treatment option (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Kuo

Chen

et al. 2021

Front. Oncol.

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BackgroundLenvatinib is approved for patients with advanced hepatocellular carcinoma (HCC) due to its non-inferiority to sorafenib of overall survival (OR) in clinical trials. This study was to compare the effectiveness and safety of lenvatinib and sorafenib in the real world.MethodsWe retrospectively evaluated 338 patients with unresectable HCC who had undergone lenvatinib or sorafenib treatment between January 2018 and August 2020. Propensity-score matching analysis was performed with a 1:2 ratio to reduce the real-life baseline difference between the two groups.ResultsA total of 210 patients (Male/Female: 150/60, mean age: 65.8 years) were recruited including 70 patients in the Lenvatinib group and 140 patients in the Sorafenib group. Compared with sorafenib, lenvatinib had significantly longer progression-free survival (PFS) (5.2 vs 3.3 months, p=0.019) but similar OR (13.3 vs 11.8 months, p=0.714). Additionally, lenvatinib had better disease control rates (62.3 vs 48.6%, p=0.029) and equivalent incidences of treatment-related adverse events over sorafenib. In multivariate analysis, lenvatinib was associated with better PFS over sorafenib (hazard ratio: 0.49, 95% confidence interval: 0.3–0.79, p=0.004) after adjustments of albumin-bilirubin grade and alpha-fetoprotein level; however, different agents using lenvatinib or sorafenib did not contribute to OS, whether in univariate or multivariate analysis. Patients who failed lenvatinib had a lower proportion of having sequential systemic therapies compared with the Sorafenib group (36.2 vs 47.8%, p=0.02). The most frequently used sequential therapy following lenvatinib and sorafenib was chemotherapy (n=9, 42.8%) and regorafenib (n=33, 50.8%), respectively.ConclusionsIn clinical real-life practice, lenvatinib illustrated promising survival benefits and acceptable safety for patients with unresectable HCC, while reducing the risk of progression disease compared with sorafenib. Additionally, lack of approved post-lenvatinib systemic therapies is a serious issue in the real world.

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Section: Introductionmentioning

confidence: 99%

Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Kuo

Chen

et al. 2021

Front. Oncol.

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“…Th2 cells secrete interleukin-4 and 10, promoting tumor growth and inducing metastasis via immunosuppression. 52–55 A Th1/Th2 imbalance has been observed in HCC patients with elevated Th2-released cytokines. 56 The dysfunction of DCs will result in the suppression of CD8+ T cell responses, leading to immune tolerance and cancer immunosurveillance failure.…”

Section: Discussionmentioning

confidence: 99%

HSPB11 is a Prognostic Biomarker Associated with Immune Infiltrates in Hepatocellular Carcinoma

Liu¹,

Yang²,

Dong³

2022

IJGM

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Purpose Heat shock proteins (HSPs) play important roles in oncogenesis and malignant progression. HSPB11 is highly expressed in many malignant tumors, but research on its role in hepatocellular carcinoma (HCC) is insufficient. Patients and Methods A comprehensive analysis of HSPB11 in HCC was performed based on data of patients with HCC and those from online public databases. Results HSPB11 was overexpressed in HCC, with a high discrimination ability between tumor and normal tissues (area under the curve =0.923). HSPB11 overexpression correlated with advanced tumor stage, poorer tumor differentiation, and worse prognosis and was an independent risk factor for HCC prognosis. The nomogram and calibration models composed of HSPB11, T stage, and M stage had good abilities to predict the 1-, 3-, and 5-year survival rates of patients. HSPB11 was determined to be involved in multiple oncogenic processes, including cell cycle checkpoints, the G2M checkpoint, E2F targets, Rho GTPases, and KRAS signaling. HSPB11 expression was related to immune cell infiltration, especially that of Th2 cells and dendritic cells. Conclusion HSPB11 is involved in oncogenesis and immune regulation in HCC and is a potential prognostic biomarker and therapeutic target.

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“…After years of sorafenib predominance and desolated perspectives, the skyline of systemic therapies for unresectable advanced HCC has considerably grown in the last decade. Not only more angiogenesis-and proliferation pathway-directed targeted therapies are available (TKIs; monoclonal antibodies), covering the therapeutic scenario from the first-to the third-line of treatment [109], but also ICIs are now well-established active agents and are gaining growing attention in the context of liver cancer [5]. Immuno-oncology (IO) represents a major breakthrough in this context, leading to a significant increase in median overall survival (OS) and to the possibility of long-term survival [110].…”

Section: Immunotherapy In Hccmentioning

confidence: 99%

Liquid Biopsy in Hepatocellular Carcinoma: Opportunities and Challenges for Immunotherapy

Maravelia

Silva

Rovesti

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC) is one of the deadliest cancer types worldwide. HCC is often diagnosed at a late stage when the therapeutic options are very limited. However, even at the earlier stages, the best treatment is liver transplantation, surgical resection or ablation. Surgical resection and ablation may carry a high risk of tumor recurrence. The recent introduction of immunotherapies resulted in clinical responses for a subgroup of patients, but there were still no effective predictive markers for response to immunotherapy or for recurrence after surgical therapy. The identification of biomarkers that could correlate and predict response or recurrence would require close monitoring of the patients throughout and after the completion of treatment. However, this would not be performed efficiently by repeated and invasive tissue biopsies. A better approach would be to use liquid biopsies including circulating tumor DNA (ctDNA), circulating RNA (e.g., microRNAs), circulating tumor cells (CTC) and extracellular vesicles (EVs) (e.g., exosomes) for disease monitoring in a non-invasive manner. In this review, we discuss the currently available technology that can enable the use of liquid biopsy as a diagnostic and prognostic tool. Moreover, we discuss the opportunities and challenges of the clinical application of liquid biopsy for immunotherapy of HCC.

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The Growing Skyline of Advanced Hepatocellular Carcinoma Treatment: A Review

Cited by 9 publications

References 113 publications

Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis

HSPB11 is a Prognostic Biomarker Associated with Immune Infiltrates in Hepatocellular Carcinoma

Liquid Biopsy in Hepatocellular Carcinoma: Opportunities and Challenges for Immunotherapy

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