Durvalumab: an investigational agent for unresectable hepatocellular carcinoma

Maestri, Marta; Pallozzi, Maria; Santopaolo, Francesco; Cerrito, Lucia; Pompili, Maurizio; Gasbarrini, Antonio; Ponziani, Francesca Romana

doi:10.1080/13543784.2022.2033208

Cited by 10 publications

(6 citation statements)

References 111 publications

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“…Systemic therapy with multiple targeted tyrosine kinase inhibitors (TKIs), including sorafenib, lenvatinib, regorafenib, and cabozantinib as well as, anti-PD-1 and anti-CTLA-4 immunotherapy, has been widely used to treat HCC ( Table 2 ) [ 54 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. Targeting the metabolites of sphingolipid metabolic pathways, such as S1PR, is also a potential therapeutic strategy for HCC [ 101 ].…”

Section: Sphingolipid Metabolic Pathway In Hcc Therapymentioning

confidence: 99%

Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy

Nojima,

Shimizu,

Murakami

et al. 2024

Cancers

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The sphingolipid metabolic pathway, an important signaling pathway, plays a crucial role in various physiological processes including cell proliferation, survival, apoptosis, and immune regulation. The liver has the unique ability to regenerate using bioactive lipid mediators involving multiple sphingolipids, including ceramide and sphingosine 1-phosphate (S1P). Dysregulation of the balance between sphingomyelin, ceramide, and S1P has been implicated in the regulation of liver regeneration and diseases, including liver fibrosis and hepatocellular carcinoma (HCC). Understanding and modulating this balance may have therapeutic implications for tumor proliferation, progression, and metastasis in HCC. For cancer therapy, several inhibitors and activators of sphingolipid signaling, including ABC294640, SKI-II, and FTY720, have been discussed. Here, we elucidate the critical roles of the sphingolipid pathway in the regulation of liver regeneration, fibrosis, and HCC. Regulation of sphingolipids and their corresponding enzymes may considerably influence new insights into therapies for various liver disorders and diseases.

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Section: Sphingolipid Metabolic Pathway In Hcc Therapymentioning

confidence: 99%

Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy

Nojima,

Shimizu,

Murakami

et al. 2024

Cancers

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“…The combination group led to grade 3/4 AEs in 25.8% of patients, durvalumab in 12.9% and sorafenib in 36.9% of patients [ 34 ]. Therefore, durvalumab and tremelimumab combination is a promising first-line option for patients who are not suitable for atezolizumab and bevacizumab, such as in the scenario with elevated bleeding risk [ 35 ].…”

Section: Systemic Therapies For Advanced Hccmentioning

confidence: 99%

Drug Treatment for Advanced Hepatocellular Carcinoma: First-Line and Beyond

Feng

Chan²,

Chan

2022

Current Oncology

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Hepatocellular carcinoma (HCC) has high mortality. The option of systemic therapy has increased significantly over the past five years. Sorafenib was the first multikinase inhibitor, introduced in 2007, as a treatment option for HCC, and it was the only effective systemic treatment for more than ten years. It was not until 2017 that several breakthroughs were made in the development of systemic strategies. Lenvatinib, another multikinase inhibitor, stood out successfully after sorafenib, and has been applied to clinical use in the first-line setting. Other multikinase inhibitors such as regorafenib, ramucirumab and cabozantinib, were approved in quick succession as second-line therapies. Concurrently, immune checkpoint inhibitors (ICIs) have readily become established treatments for many solid tumors, including HCC. The most studied ICIs to date, target programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). These ICIs have demonstrated efficacy in treating advanced HCC. More recently, combination of bevacizumab and atezolizumab (ICI targeting PD-L1) was approved as the gold-standard first-line therapy. Combination of ICIs with nivolumab and ipilimumab was also approved in the second-line setting for those who failed sorafenib. At the moment, numerous clinical trials in advanced HCC are underway, which will bring continuous change to the management, and increase the survival, for patients with advanced HCC. Our review article: (1) summarizes United States Food and Drug Administration (US FDA) approved systemic therapies in advanced HCC, (2) reports the evidence of currently approved treatments, (3) discusses potential drugs/drug combinations being currently tested in phase III clinical trials, and (4) proposes possible future directions in drug development for advanced HCC.

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“…Combination of Durvalumab, an anti PD-L1 antibody, and Tremelimumab, an anti CTLA-4 antibody, was superior to Sorafenib in terms of OS either in combination or as Durvalumab monotherapy [ 61 , 75 ]. A phase-Ib trial [/NCT04605731] will evaluate the safety of Durvalumab plus Tremelimumab or Durvalumab alone after SIRT in patients with unresectable locally advanced BCLC B/C HCC with Child–Pugh A and tumor burden < 50% in terms of ORR according to RECIST, mRECIST and immune mRECIST criteria.…”

Section: Combination Of Tare With Immunotherapymentioning

confidence: 99%

Section: Combination Of Tare With Immunotherapymentioning

confidence: 99%

SIRT in 2025

Ponziani¹,

Santopaolo²,

Posa

et al. 2022

Cardiovasc Intervent Radiol

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Selective internal radiation therapy represents an endovascular treatment option for patients with primary liver malignancies, in different clinical stages. Potential applications of this treatment are in early-stage hepatocellular carcinoma, as a curative option, or in combination with systemic treatments in intermediate and advanced-stages. This review, based on existing literature and ongoing trials, will focus on the future of this treatment in patients with hepatocellular carcinoma, in combination with systemic treatments, or with the use of new devices and technological developments; it will also describe new potential future indications and structural and organizational perspectives.

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Durvalumab: an investigational agent for unresectable hepatocellular carcinoma

Cited by 10 publications

References 111 publications

Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy

Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy

Drug Treatment for Advanced Hepatocellular Carcinoma: First-Line and Beyond

SIRT in 2025

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