Browse
Submit Data
Databases
API
Help

Dataset Information

34 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The future is now: beyond first line systemic therapy in hepatocellular carcinoma

ABSTRACT: Hepatocellular carcinoma (HCC) is becoming a worldwide concern due to its rising incidence. Although for the incipient stages there are curative therapies, the advanced disease represents a major provocation for the clinicians. 2008 marked as an important year for the hepatology community with the administration of sorafenib for late stages of HCC. Six years after this major discovery, the multikinase inhibitor still represents an important pillar, the first line treatment for the advanced liver cancer. Lenvatinib may represent a new promising first line strategy, but it is still unavailable in many countries. The last years represented an explosion in the research of HCC. Beyond the first line treatments there are a plethora of new emerging therapies. By far immunotherapy represents the major revolution in oncology. While adoptive immunotherapy is still at the beginning, immune check-point inhibitors bursted in many clinical trials with very encouraging results. This review summarises the major discoveries in the field of HCC with an emphasis on immunotherapy. It also briefly describes the important aspects of primary liver cancer immunology and the major ongoing clinical trials.

SUBMITTER: Nenu I

PROVIDER: S-EPMC8797356 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Beyond First-Line Immune Checkpoint Inhibitor Therapy in Patients With Hepatocellular Carcinoma.

Project description:Until recently, the treatment landscape for hepatocellular cancer (HCC) was dominated by tyrosine kinase inhibitors (TKIs) which offered an overall survival (OS) benefit when used both in the first-and second-line setting compared to best supportive care. However, the treatment landscape has changed with the introduction of immune checkpoint inhibitors (ICIs) for the treatment of HCC with significant improvement in OS and progression free survival reported with combination atezolizumab and bevacizumab compared to sorafenib in the first-line setting. Nonetheless, the response to ICIs is 20-30% and invariably patients will progress. What remains unclear is which therapeutics should be used following ICI exposure. Extrapolating from the evidence base in renal cell carcinoma, subsequent therapy with TKIs offers both a response and survival benefit and are recommended by European guidelines. However, there are a number of novel therapies emerging that target mechanisms of ICI resistance that hold promise both in combination with ICI or as subsequent therapy. This paper will discuss the evidence for ICIs in HCC, the position of second-line therapies following ICIs and research strategies moving forward.

| S-EPMC8005707 | biostudies-literature

Optimizing systemic therapy for metastatic renal cell carcinoma beyond the first-line setting.

Project description:The introduction of molecularly targeted therapies (TTs) has transformed the management of metastatic renal cell carcinoma (mRCC). Within a relatively short period of time, systemic treatment of mRCC has evolved from a disease treated only by cytokines to a disease where TT is the cornerstone of patient management. Since the approval of sorafenib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), in December 2005, 7 drugs have been introduced that have provided a high level of clinical efficacy in patients with mRCC, with a median survival of ~30 months in an unselected patient population that generally fits trials eligibility. Despite such success, advancements in therapies have reached a plateau: different combinations of targeted agents have not demonstrated additional benefit mainly owing to toxicity concerns, and some novel agents have failed to show benefit over approved drugs in clinics. In this review, we aim to focus on optimizing selection of agents in mRCC after progression on first-line TT. We also review how new drugs may transform existing guidelines and break through the current plateau reached with approved agents.

| S-EPMC4654640 | biostudies-literature

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

Project description: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.

| S-EPMC9406660 | biostudies-literature

Role of Systemic Therapy and Future Directions for Hepatocellular Carcinoma.

Project description:Hepatocellular carcinoma (HCC) is an aggressive tumor that often arises in the setting of liver cirrhosis. Although early-stage disease is often amenable for surgical resection, transplant, or locoregional therapies, many patients are diagnosed at an advanced stage or have poor liver reserve. Systemic therapy is the mainstay of treatment for these patients. At present, the only approved therapy for the treatment of advanced disease is the tyrosine multikinase inhibitor sorafenib. Candidacy for treatment is based on liver reserve. Novel agents for the treatment of this disease are urgently needed. In this article, we review systemic therapy trials and upcoming data for the treatment of HCC.

| S-EPMC5937243 | biostudies-other

Systemic therapy of hepatocellular carcinoma: current status and future perspectives.

Project description:The management of hepatocellular carcinoma (HCC) has substantially changed in the past few decades, the introduction of novel therapies (such as sorafenib) have improved patient survival. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. Decision-making largely relies on evidence-based criteria, as showed in the US and European clinical practice guidelines, which endorse five therapeutic recommendations:resection; transplantation; radiofrequency ablation; chemoembolization; and sorafenib. Many molecularly targeted agents that inhibit angiogenesis, epidermal growth factor receptor, and mammalian target of rapamycin are at different stages of clinical development in advanced HCC. Future research should continue to unravel the mechanism of hepatocarcinogenesis and to identify key relevant molecular targets for therapeutic intervention. Identification and validation of potential surrogate and predictive biomarkers hold promise to individualize patient's treatment to maximize clinical benefit and minimize the toxicity and cost of targeted agents.

| S-EPMC3964381 | biostudies-other

Systemic therapy in hepatocellular carcinoma.

Project description:Many potential systemic therapies are being investigated for the treatment of hepatocellular carcinoma (HCC). The incidence of this malignancy is rising sharply and the vast majority of patients present at advanced stages. Although the earlier dismal results with cytotoxic chemotherapies made way for the development of locoregional therapies that provided improved overall survival, truly personalized therapy will require the selection of phenotypically similar stages of disease and populations, an understanding of the complex molecular and genetic pathways leading to HCC, and a keen understanding of the pathobiology of cirrhosis. Only then will we understand how to offer a particular patient at a specific stage of disease the appropriate therapy to truly prolong survival.

| S-EPMC3758582 | biostudies-other

Lenvatinib Beyond First-Line Therapy in Patients With Advanced Biliary Tract Carcinoma.

Project description:IntroductionLenvatinib, a multiple receptor tyrosine kinase inhibitors that target vascular endothelial growth factor receptors and fibroblast growth factor receptors, recently demonstrated a treatment effect in various tumors. This study evaluated the efficacy and safety of lenvatinib for patients with biliary tract cancers (BTCs) who had received ≥1 line of prior systemic anti-BTC therapy.MethodsThis open-label, single-arm study included adult (≥18 years) patients with histologically confirmed BTC. Efficacy and safety were evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1) and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Changes in tumor biomarkers throughout the treatment period were recorded.Results41 patients received lenvatinib treatment. The ORR was 12% (95% CI: 1.7-22.7), with a median PFS of 3.8 months (95% CI: 1.3-6.3) and an OS of 11.4 months (95% CI: 6.6-16.2). Thirty-nine (95.1%) patients experienced ≥1 treatment-related adverse event. Decreasing carbohydrate antigen 19-9 (CA19-9) level predicted tumor size reduction in intrahepatic cholangiocarcinoma with a sensitivity of 77.7% and a specificity of 73.9%.ConclusionsLenvatinib which was individualized based on the patient's weight has promising clinical activity against advanced BTC and had an acceptable safety profile. Additionally, serum biomarkers and gene sequencing may hold the potential to guide our treatment.

| S-EPMC8928459 | biostudies-literature

First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma-An Update on Patient Selection and Response Evaluation.

Project description:Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) is helpful to identify patients who do not benefit from sorafenib treatment.

| S-EPMC5192519 | biostudies-literature

Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment.

Project description:Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate second-line systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.

| S-EPMC10035683 | biostudies-literature

Systemic therapy for hepatocellular carcinoma.

Project description:Optimal treatment of hepatocellular carcinoma (HCC) is clinically challenging. Systemic treatment for advanced HCC was limited until the approval of sorafenib. This discovery resulted in the advent of many clinical trials. An ongoing Phase III trial is examining the benefit of adjuvant sorafenib. Utilization of doxorubicin-eluting bead embolization may offer safer treatment in eligible HCC patients. The use of systemic treatment peritransarterial chemoembolization is also being investigated. Many targeted therapies are being explored as first-/second-line treatment options in advanced HCC. The potential benefit of c-MET inhibitors, particularly in those with advanced, MET high expression HCC, may result in new systemic patient-directed targeted medicinal approaches. Remaining dilemmas query the appropriate management of patients with advanced Child-Pugh B, HCC and those recurring post-transplant.

| S-EPMC6114012 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data