Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Second-line treatment options in hepatocellular carcinoma.

ABSTRACT: For many years, sorafenib has been the only approved systemic treatment for advanced hepatocellular carcinoma (HCC). For over a decade, randomized controlled trials exploring the efficacy of new drugs both in first- and second-line treatment have failed to prove any survival benefit. However, in the past few years, several advances have been made especially in pretreated patients; phase III trials of regorafenib, cabozantinib, and ramucirumab in patients with elevated ?-fetoprotein have demonstrated efficacy in patients progressing after or intolerant to sorafenib. In addition, early phase I and II trials have shown promising results of immunotherapy alone or in combination with tyrosine-kinase inhibitors or monoclonal antibodies in the same setting of patients. In this review, we will discuss the evidence on second-line options for HCC, focusing on the latest results that are currently refining the treatment scenario.

SUBMITTER: Marino D

PROVIDER: S-EPMC6469745 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Second-line treatment options in hepatocellular carcinoma.

Marino Donatella D Zichi Clizia C Audisio Marco M Sperti Elisa E Di Maio Massimo M

Drugs in context 20190410

For many years, sorafenib has been the only approved systemic treatment for advanced hepatocellular carcinoma (HCC). For over a decade, randomized controlled trials exploring the efficacy of new drugs both in first- and second-line treatment have failed to prove any survival benefit. However, in the past few years, several advances have been made especially in pretreated patients; phase III trials of regorafenib, cabozantinib, and ramucirumab in patients with elevated α-fetoprotein have demonstr ...[more]

PMID: 31024634

Similar Datasets

Second-Line Treatment Options for Hepatocellular Carcinoma: Current Landscape and Future Direction.

Project description:Hepatocellular carcinoma is a leading cause of mortality worldwide, and its incidence is rising. The last few years have witnessed a proliferation of available systemic therapeutic options, with the approval of multiple agents, including immune checkpoint inhibitors and drugs targeting vascular endothelial growth factor, such as cabozantinib, regorafenib, and ramucirumab. Most recently, the combination of atezolizumab plus bevacizumab has resulted in the longest overall survival yet known in hepatocellular carcinoma, therefore changing the preferred first-line treatment from the previous options of sorafenib and lenvatinib. The aim of this review is to summarize the available clinical data for the current second-line systemic treatment options and the future perspectives in the treatment landscape of hepatocellular carcinoma.

| S-EPMC8464222 | biostudies-literature

Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma.

Project description:Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC.

| S-EPMC5036543 | biostudies-literature

Targeted agents for second-line treatment of advanced hepatocellular carcinoma.

Project description:Over the past ten years, sorafenib, a multikinase inhibitor, has been the standard of care for patients with unresectable hepatocellular carcinoma (HCC) and well-preserved liver function. Recently, lenvatinib, a different multikinase inhibitor, was shown to be non-inferior to sorafenib, in terms of survival, while all other agents previously tested failed to prove non-inferiority (or superiority) when compared to sorafenib. Similarly, in the second-line setting, most investigational drugs failed to provide better survival outcomes than placebo. However, in the last 2 years three positive phase III trials have been published in this setting. The RESORCE trial, a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib, showed better outcomes with regorafenib compared to placebo. More recently, the phase III CELESTIAL trial demonstrated the superiority of cabozantinib, a multikinase inhibitor targeting vascular endothelial growth factor receptor, MET, and AXL, vs placebo in the second- and third-line setting in patients progressing on or intolerant to sorafenib. The survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein levels. Overall, the adverse events reported in these trials were in line with the known safety profiles of the tested agents. After nearly a decade of a certain degree of stagnation, we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC.

| S-EPMC6815920 | biostudies-literature

Defining the Ideal Patient with Hepatocellular Carcinoma for Second-Line Treatment.

Project description:Background:Second line of treatment of hepatocellular carcinoma (HCC) has notably changed in recent years as three novel drugs with a different mechanism of action have demonstrated to improve survival compared to placebo; thus, there is a need to better define the profile of optimal candidates to second-line treatment with these drugs in order to maximize clinical benefit. Materials and Methods:We performed a pooled analysis from the subgroup analysis of all published phase III trials for approved targeted therapy in the second line of treatment for HCC, with the aim to discover possible clinical-pathological predictive factors. Results:Four studies were included in the analysis for a total of 2137 cases whose results supported the use of these novel agents in male patients with ECOG: 0, extrahepatic metastases, and HBV infection. Conclusions:Future studies are awaited to define best candidates for novel agents approved in the second line of treatment for HCC.

| S-EPMC7321521 | biostudies-literature

Systemic Treatment Options in Hepatocellular Carcinoma.

Project description:Background:Patients with advanced hepatocellular carcinoma (HCC) typically have poor survival outcomes. Until recently, sorafenib was the only systemic therapy option available and no agents were approved after sorafenib failure. However, rapid changes are beginning to emerge in the treatment landscape of advanced HCC, with approvals of regorafenib, nivolu-mab, lenvatinib, pembrolizumab, and cabozantinib and positive phase II/III clinical trial results with other agents. Summary:Here, we provide a comprehensive overview of the clinical trial data of systemic agents that are currently approved for advanced HCC (sorafenib, regorafenib, and nivolumab), including agents recently approved in 2018 (lenvatinib, pembrolizumab, and cabozantinib) and those with recent positive phase II/III results (ramucirumab). Key features of the clinical trial design, including patient selection criteria, the use of biomarkers in HCC, and criteria for efficacy assessment, and their implications in real-world practice are discussed. Important ongoing and planned trials in advanced HCC are summarized to provide a glimpse into the future of advanced HCC treatment. From a physician's viewpoint, the treatment algorithms for advanced HCC are undergoing significant changes, as additional and imminent approvals impact the choices of first- and second-line treatment and decisions regarding the timing of therapy initiation. With these additional choices at hand, treatment sequencing remains a complex task and should take patient selection and tolerance profiles into account. Key Messages:The treatment of advanced HCC remains challenging and complex. The rapid developments in systemic therapy for advanced HCC should be considered when determining the best choice and sequence of treatment for patients with advanced HCC.

| S-EPMC6883446 | biostudies-literature

Navigating the new landscape of second-line treatment in advanced hepatocellular carcinoma.

Project description:Sorafenib and lenvatinib are approved for first-line treatment of patients with advanced hepatocellular carcinoma (HCC), and the efficacy of atezolizumab plus bevacizumab has been demonstrated versus sorafenib. Over time, first-line treatment frequently fails, and regorafenib, cabozantinib, ramucirumab (for patients with alpha fetoprotein ?400 ng/mL), nivolumab, pembrolizumab and ipilimumab plus nivolumab are approved for use after sorafenib (but not lenvatinib) treatment in advanced HCC. Given the considerable complexity in the therapeutic landscape, the objective of this review was to summarize the clinical evidence for second-line agents and provide practical guidance for selecting the best sequential treatment approach. The timing and sequencing of treatment switches are key to optimizing patient outcomes in advanced HCC, and decisions should be informed by reasons for discontinuation of previous therapy and disease progression. It is important not to switch too soon, because sequential treatment benefit may then be lost, nor should switching be delayed too long. Effectiveness, safety and tolerability, patient quality of life, route of administration, dosing regimen, drug class, molecular target and individual patients' characteristics, including comorbidities, inform the selection of second-line systemic treatment, independently of the aetiology of HCC, tumour stage and the response to previous treatment. Biomarkers predictive of treatment effectiveness are of great value, but currently biomarker-driven patient selection is possible only in the case of ramucirumab. The approval of new combination therapies for advanced HCC in the first-line setting will further increase the complexity of decision-making. However, the important factors will remain the individual patient's characteristics and preferences.

| S-EPMC7496898 | biostudies-literature

Novel therapeutic options for second-line therapy in metastatic renal cell carcinoma.

Project description:Metastatic renal cell carcinoma (mRCC) has gained a variety of therapeutic options since the introduction of targeted therapy, starting in 2007. The basic molecular mechanisms included predominantly the targeting of vascular endothelial growth factor or the inhibition of the mammalian target of rapamycin. Recently, results from two randomized controlled trials, the CheckMate-25 and the METEOR trial, regarding therapy for RCC in the second-line setting have been published. In the present review, the current status of second-line therapy in mRCC is discussed, together with results from the two newly introduced substances, nivolumab and cabozantinib.

| S-EPMC4888023 | biostudies-literature

Sorafenib as second-line treatment option after failure of lenvatinib in patients with unresectable hepatocellular carcinoma.

Project description:Background and aimCurrently, there is no molecular-targeted agent that has demonstrated evidence of efficacy in patients with unresectable hepatocellular carcinoma (u-HCC) who have developed resistance to treatment with lenvatinib (LEN). In this real-world study, we aimed to investigate the therapeutic effect and safety of sorafenib (SOR) in patients with u-HCC after progression on treatment with LEN.Methods patients and resultsA total of 13 patients with u-HCC (12 males and 1 female), who were treated with SOR after progression on LEN, were enrolled in this retrospective study. Therapeutic efficacy was evaluated via contrast-enhanced computerized tomography at 8 weeks after the initiation of SOR therapy according to modified response evaluation criteria in solid tumors (mRECIST) and RECIST. According to mRECIST, the objective response rate (ORR) and disease control rate (DCR) were 15.3% (2/13) and 69.2% (9/13), respectively. According to RECIST, the ORR and DCR were 0% (0/13) and 69.2% (9/13), respectively. The median progression-free survival was 4.1 months. The median albumin-bilirubin scores did not deteriorate significantly at 4, 6, and 8 weeks after initiation of SOR, compared with the scores at the baseline. The most frequent grade 1 or 2 adverse events (AEs) were palmar-plantar erythrodysesthesia, fatigue, diarrhea, and hypertension. There was no incidence of grade 3 AEs.ConclusionTreatment with SOR may be effective for u-HCC after failure on LEN and may not worsen the liver reserve.

| S-EPMC7731817 | biostudies-literature

Treatment options after sorafenib failure in patients with hepatocellular carcinoma.

Project description:Second line therapy after failure of sorafenib continues to be under study. Prognosis of hepatocellular carcinoma is measured in months, with median overall survival reaching 10.7 months with sorafenib. Because of the modest net benefit sorafenib has contributed, and rising incidence of hepatocellular carcinoma in the world, continued efforts are ongoing to look for efficient upfront, second line, or combination therapies. Herein we review the most relevant to date published literature on treatment options beyond sorafenib, reported studies, ongoing investigational efforts, and possibilities for future studies in advanced hepatocellular carcinoma.

| S-EPMC5760005 | biostudies-literature

Treating hepatocellular carcinoma progression following first-line sorafenib: therapeutic options and clinical observations.

Project description:Despite the established efficacy of sorafenib in advanced hepatocellular carcinoma (HCC), a significant number of sorafenib-treated patients experience disease progression. Current guidelines recommend either best supportive care or clinical trial enrollment for this population. As such, there remains an unmet need for tolerable, life-prolonging strategies in the second-line setting. New information regarding the molecular pathogenesis of resistance to antiangiogenic therapy and positive post-progression experience with antiangiogenics in other tumor types has led to trials investigating the effect of continued use of sorafenib, alone or combined with other agents. Trials investigating the effect of switching from sorafenib to alternate antiangiogenic agents, phosphatidylinositol 3 kinase/AKT/mammalian target of rapamycin inhibitors, or cMet inhibitors are also underway. As these data emerge, clinicians may consider a new paradigm for managing advanced HCC. This article briefly reviews the mechanisms of disease resistance to antiangiogenic therapy as a vehicle for discussing clinical strategies to prolong survival in patients with advanced HCC that are currently employed at our institutions or are under investigation. Key ongoing trials investigating the use of molecularly targeted therapies in patients with progressive disease are also highlighted.

| S-EPMC3808569 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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