Frontline therapy for advanced hepatocellular carcinoma: an update

Akce, Mehmet; El‐Rayes, Bassel F.; Bekaii‐Saab, Tanios

doi:10.1177/17562848221086126

Cited by 19 publications

(13 citation statements)

References 79 publications

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“…Anti-angiogenic therapy is a promising strategy for the treatment of HCC ( Table 1 ). Sorafenib is the first TKI approved as a first-line treatment for advanced HCC 121 . Sorafenib blocks receptors involved in oncogenesis and angiogenesis, including VEGFR2, PDGFR, Raf-1, c-Kit, FLT3, and RET.…”

Section: Anti-angiogenic Therapies In Hcc Angiogenesismentioning

confidence: 99%

Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies

Yao

Kong

et al. 2023

Cancer Biol Med

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Angiogenesis, the process of formation of new blood vessels, is required for cancer cells to obtain nutrients and oxygen. HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth, progression, invasion, and metastasis. Current anti-angiogenic therapies target mainly tyrosine kinases, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR), and are considered effective strategies for HCC, particularly advanced HCC. However, because the survival benefits conferred by these anti-angiogenic therapies are modest, new anti-angiogenic targets must be identified. Several recent studies have determined the underlying molecular mechanisms, including pro-angiogenic factors secreted by HCC cells, the tumor microenvironment, and cancer stem cells. In this review, we summarize the roles of pro-angiogenic factors; the involvement of endothelial cells, hepatic stellate cells, tumor-associated macrophages, and tumor-associated neutrophils present in the tumor microenvironment; and the regulatory influence of cancer stem cells on angiogenesis in HCC. Furthermore, we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC. A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

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Section: Anti-angiogenic Therapies In Hcc Angiogenesismentioning

confidence: 99%

Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies

Yao

Kong

et al. 2023

Cancer Biol Med

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“…HIMALAYA phase III trial data show that tremelimumab plus durvalumab can significantly improve overall survival (OS) compared with sorafenib in first-line patients with unresected HCC, regardless of baseline albumin–bilirubin (ALBI) grade. On 21 October 2022, tremelimumab in combination with durvalumab was approved by the FDA for the treatment of unresectable HCC [ 88 ].…”

Section: Immune Checkpoint Inhibitors For the Treatment Of Hbv-hccmentioning

confidence: 99%

Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy

Zhang

Xie

et al. 2023

Vaccines

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Hepatitis B virus (HBV) infection is the main risk factor for the development of hepatocellular carcinoma (HCC), the most common type of liver cancer, with high incidence and mortality worldwide. Surgery, liver transplantation, and ablation therapies have been used to treat early HBV-caused HCC (HBV-HCC); meanwhile, in the advanced stage, chemoradiotherapy and drug-targeted therapy are regularly considered, but with limited efficacy. Recently, immunotherapies, such as tumor vaccine therapy, adoptive cell transfer therapy, and immune checkpoint inhibitor therapy, have demonstrated promising efficacy in cancer treatment. In particular, immune checkpoint inhibitors can successfully prevent tumors from achieving immune escape and promote an anti-tumor response, thereby boosting the therapeutic effect in HBV-HCC. However, the advantages of immune checkpoint inhibitors in the treatment of HBV-HCC remain to be exploited. Here, we describe the basic characteristics and development of HBV-HCC and introduce current treatment strategies for HBV-HCC. Of note, we review the principles of immune checkpoint molecules, such as programmed cell death protein 1(PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in HBV-HCC, as well as related inhibitors being considered in the clinic. We also discuss the benefits of immune checkpoint inhibitors in the treatment of HBV-HCC and the efficacy of those inhibitors in HCC with various etiologies, aiming to provide insights into the use of immune checkpoint inhibitors for the treatment of HBV-HCC.

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“…However, the biggest difference between the two guidelines is that the Chinese guidelines present some reference comments for TKIs, chemotherapeutic agents combine with ICIs regimens, as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) inhibitor plus PD-1/programmed cell death ligand 1 (PD-L1) inhibitor combination regimens ( 9 ), providing additional treatment options for physicians and patients. ICI monotherapy has also been proposed as a first-line treatment option under certain circumstances, emphasizing that systemic HCC therapy has entered the immunotherapy era ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

A multi-center retrospective study on the efficacy and safety of regorafenib vs. regorafenib combined with PD-1 inhibitors as a second-line therapy in patients with advanced hepatocellular carcinoma

Yan¹,

Huang²,

Peng³

et al. 2023

Ann Transl Med

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Background At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the combination therapy of regorafenib and programmed death-1 (PD-1) inhibitors with regorafenib monotherapy as a second-line treatment for patients with advanced HCC. Methods Our multicenter retrospective study evaluated consecutive patients with advanced HCC who received regorafenib plus PD-1 inhibitors or regorafenib alone as a later-line therapy from May 2019 to January 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, and safety was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results A total of 133 patients were included in the study (regardless of first-line treatment), including 94 who received regorafenib plus PD-1 inhibitors and 39 who received regorafenib. The regorafenib plus PD-1 inhibitors group had a significantly higher ORR (25.53% vs. 10.26%, P=0.015), higher DCR (87.23% vs. 66.67%, P=0.006), and longer PFS (median 9.0 vs. 4.0 months, P<0.0001) than the regorafenib group. Meanwhile, the median OS (mOS) did not differ between the regorafenib plus PD-1 and regorafenib monotherapy groups {mOS, 14.0 months [95% confidence interval (CI), 14.0–16.0 months] vs. 12.0 months (95% CI, 10.0–22.0 months)}. There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (71.79% vs. 78.72%, P=0.39) and the incidence of grade 3/4 serious adverse effects (5.13% vs. 18.09%, P=0.19) between the regorafenib monotherapy group and PD-1 inhibitors combination group. Conclusions Compared with regorafenib alone, regorafenib combined with PD-1 inhibitors therapy increased PFS, ORR but did not improve OS, and can be used an option in second-line HCC therapy, regardless of first-line treatments. Regorafenib combined with PD-1 inhibitors is recommended as early as a second-line therapy to benefit patients. The combination regimen was as safe as regorafenib monotherapy for treatment of HCC in patients with compensated liver disease [Child-Turcotte-Pugh (CTP) A/B].

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Frontline therapy for advanced hepatocellular carcinoma: an update

Cited by 19 publications

References 79 publications

Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies

Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies

Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy

A multi-center retrospective study on the efficacy and safety of regorafenib vs. regorafenib combined with PD-1 inhibitors as a second-line therapy in patients with advanced hepatocellular carcinoma

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