scholarly journals Recent advances in systemic therapy for hepatocellular carcinoma

2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Huajun Zhang ◽  
Wuyang Zhang ◽  
Longying Jiang ◽  
Yongheng Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Targeted Therapy ◽  
Systemic Treatment ◽  
Malignant Tumors ◽  
Targeted Agents ◽  
Rapid Progress ◽  
Advanced Hcc ◽  
The Past ◽  
The World ◽  
Systemic Drug

AbstractHepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors in the world. Therapeutic options for advanced HCC are limited. Systemic treatment, especially with conventional cytotoxic drugs, is usually ineffective. For more than a decade, sorafenib has been the only systemic drug that has been proven to be clinically effective for treating advanced HCC. However, over the past three years, the rapid progress of molecular targeted therapies has dramatically changed the treatment landscape for advanced HCC. Immune checkpoint therapies are now being incorporated into HCC therapies, and their combination with molecular targeted therapy is emerging as a tool to enhance the immune response. In this review, we summarize the development and progress of molecular targeted agents and immunotherapies in HCC.

scholarly journals Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Gaetano Bertino ◽  
Shirin Demma ◽  
Annalisa Ardiri ◽  
Maria Proiti ◽  
Giulia Malaguarnera ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Web Of Science ◽  
Malignant Tumors ◽  
Tumor Staging ◽  
Treatment Options ◽  
Advanced Hcc ◽  
The Past ◽  
Dismal Prognosis ◽  
Keywords Hepatocellular Carcinoma

Background. Hepatocellular carcinoma is one of the most common and lethal malignant tumors worldwide. Over the past 15 years, the incidence of HCC has more than doubled. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with HCC. A better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy. Materials and Methods. A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” and “immunotherapy.” Discussion and Conclusion. Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension, and the underlying degree of liver dysfunction. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.

scholarly journals New agents on the horizon in hepatocellular carcinoma

2012 ◽  
Vol 5 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Andrew X. Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Iii ◽  
Current Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Targeted Agents ◽  
New Agents ◽  
The Past ◽  
Early Evidence ◽  
Molecularly Targeted Agents ◽  
Active Research

Despite the successful approval and extensive application of sorafenib, the prognosis for patients with advanced hepatocellular carcinoma (HCC) remains poor. Fortunately, there have been renewed and continued interests and active research in developing other molecularly targeted agents in HCC during the past few years. While there is early evidence of antitumor activity of several agents in phase I/II studies, phase III efforts with a few targeted agents have failed, highlighting the challenges of new drug development in HCC. This review summarizes the current status of other molecularly targeted agents under development in advanced HCC.

scholarly journals Targeted Therapies in the Treatment of Advanced Hepatocellular Carcinoma

2013 ◽  
Vol 7 ◽  
pp. CMO.S7633 ◽  
Author(s):  
Zhengyu Wei ◽  
Cataldo Doria ◽  
Yuan Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapies ◽  
Recent Progress ◽  
Systemic Treatment ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The Third ◽  
Promising Target ◽  
Targeted Treatments ◽  
Attractive Option

Hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer death. It has been a major worldwide health problem with more new cases being diagnosed each year. The current available therapies for patients with advanced HCC are extremely limited. Therefore, it is of great clinical interests to develop more effective therapies for systemic treatment of advanced HCC. Several promising target-based drugs have been tested in a number of clinical trials. One breakthrough of these efforts is the approved clinical use of sorafenib in patients with advanced HCC. Targeted therapies are becoming an attractive option for the treatment of advanced HCC. In this review, we summarize the most recent progress in clinical targeted treatments of advanced HCC.

scholarly journals SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE

2016 ◽  
Vol 29 (4) ◽  
pp. 276-278 ◽  
Author(s):  
Luiza Vitelo ANDRIGHETTO ◽  
◽  
Aline Kirjner POZIOMYCK ◽  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Adipose Tissue ◽  
Key Words ◽  
Malignant Tumors ◽  
Review Article ◽  
Review Of The Literature ◽  
Serum Leptin ◽  
The World ◽  
The Relationship

ABSTRACT Introduction: Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. Objective: To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Method: Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. Results: After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Conclusion: Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported.

scholarly journals Management of hepatocellular carcinoma after progression on first-line systemic treatment: defining the optimal sequencing strategy in second line and beyond

2020 ◽  
Vol 27 (S3) ◽  
Author(s):  
C.P. Amaro ◽  
V.C. Tam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systemic Treatment ◽  
Treatment Algorithm ◽  
Current Data ◽  
Second Line ◽  
First Line ◽  
Optimal Sequencing ◽  
The World ◽  
Sequencing Strategy ◽  
Line Setting

    Hepatocellular carcinoma (hcc) is one of the most common cancers in the world. It has a high mortality rate, espe­cially when localized treatments fail. For about a decade, the only systemic treatment shown to improve survival was sorafenib. Recently, lenvatinib was found to be noninferior to sorafenib for overall survival and the combination atezolizumab–bevacizumab improved survival compared with sorafenib. Similarly, in the post-sorafenib setting, a number of recent positive clinical trials have been reported, and they indicate that regorafenib, cabozantinib, and ramucirumab are effective and safe in the second-line setting.     With so many new options available, including immunotherapy, it is challenging to define the best sequence of systemic treatment for patients with hcc. In the present review, we introduce the current data for second-line sys­temic treatment and beyond in hcc. A treatment algorithm is also suggested, based on the best available evidence and expert opinion.

scholarly journals Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 526 ◽  
Author(s):  
Alqahtani ◽  
Khan ◽  
Alloghbi ◽  
Said Ahmed ◽  
Ashraf ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Advanced Hcc ◽  
Complex Process ◽  
Clinical Benefits ◽  
Approved Drugs

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors worldwide. HCC is a complex process that is associated with several etiological factors, which in turn result in aberrant activation of different cellular and molecular pathways and the disruption of balance between activation and inactivation of protooncogenes and tumor suppressor genes, respectively. Since HCC most often occurs in the setting of a diseased or cirrhotic liver and most of the patients are diagnosed at the late stage of disease, prognosis is generally poor. At present, limited treatment options with marginal clinical benefits are available. Systemic therapy, particularly in the form of conventional cytotoxic drugs, are generally ineffective. In recent years, molecular-targeted therapies have been clinically used to treat various cancers, including liver cancer. This approach inhibits the growth of tumor cells by interfering with molecules that are involved in carcinogenesis, which makes it more selective and specific than cytotoxic chemotherapy. Many clinical trials have been carried out while using molecular targeted drugs in advanced HCC with many more in progress. The clinical trials in HCC to date have evaluated a single-targeted therapy alone, or two or more targeted therapies in parallel. The aim of this review is to provide insight of various molecular mechanisms, leading to HCC development and progression, and also the range of experimental therapeutics for patients with advanced HCC. The review will summarize different clinical trials data the successes and failures of these treatments, as well as the most effective and approved drugs designed against HCC.

A Review of the Management of Hepatocellular Carcinoma: Standard Therapy and a Look to New Targets

2012 ◽  
pp. 275-280
Author(s):  
Andrew X. Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Options ◽  
Mechanisms Of Action ◽  
Targeted Agents ◽  
Adjuvant Setting ◽  
Advanced Hcc ◽  
Molecularly Targeted Agents ◽  
Drug Eluting Beads ◽  
Drug Eluting ◽  
New Treatment

Overview: Management of hepatocellular carcinoma (HCC) continues to be challenging, but new treatment options are evolving. A multidisciplinary evaluation will help make the best treatment decisions for each patient. Although we continue to improve the outcomes of curative treatment with resection, liver transplant, and radiofrequency ablation (RFA), many new liver-directed regional therapies including drug-eluting beads, radioembolization, and radiation are emerging. Sorafenib remains the only approved agent for advanced HCC, and its role in the adjuvant setting following resection or RFA, with transarterial chemoembolization, or in combination with other targeted agents or chemotherapy in the advanced stage is under investigation. Many molecularly targeted agents with novel mechanisms of action are under active development.

Response of advanced HCC to pembrolizumab and lenvatinib combination therapy despite monotherapy failure

2020 ◽  
Vol 58 (08) ◽  
pp. 773-777 ◽  
Author(s):  
Nadine Schulte ◽  
Moying Li ◽  
Tianzuo Zhan ◽  
Lena Dreikhausen ◽  
Janina Sollors ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The World ◽  
Vegf Inhibition ◽  
Tki Treatment

AbstractIn recent years, immune checkpoint inhibitors (ICIs) were successfully introduced to cancer therapy, and these drugs have already become essential for the treatment of various noncurable tumors. However, monotherapy in advanced hepatocellular carcinoma (aHCC) failed to show statistically significant improvement.Recently, the combination of atezolizumab and bevacizumab demonstrated efficacy of combining ICI and VEGF inhibition, further substantiating previous data on synergistic mechanisms among respective substance classes.As TKI treatment is currently standard of care for aHCC, and ICIs are approved by the FDA and available in many areas of the world, numerous patients may have been treated with monotherapy of those drugs. However, it remains unclear if failure to monotherapy has an impact on combination therapy. We therefore report a patient well responding to combination therapy despite previous failures to TKI and ICI monotherapy.

Surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: Meta-analysis of randomized controlled trials.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 454-454
Author(s):  
Kyung-Hun Lee ◽  
Dae-Won Lee ◽  
Myoung-Jin Jang ◽  
Tae-Yong Kim ◽  
Sae-Won Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Molecular Targeted Therapy ◽  
Treatment Effects ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Incremental Benefit ◽  
Randomized Controlled

454 Background: Time to progression (TTP) is suggested as a reliable endpoint compared to progression free survival (PFS) in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied. Methods: We searched Pubmed and Embase data to obtain data source. Eligible studies were randomized controlled phase III trials which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association of treatment effects as shown by the hazard ratio (HR) of TTP and OS in each trial was assessed by Spearman rank correlation coefficient ( rs) and linear regression analysis. The association between median TTP and OS was also investigated. Results: Nine studies with a total of 18 treatment arms and 6318 patients were included. Incremental benefit from the study treatment in TTP from each trial was correlated with incremental benefit in OS. The rs value and R2 value between log (HRTTP) and log (HROS) was 0.73 (95% CI 0.12 – 0.94, p = 0.024) and 0.57. The minimum TTP effect to predict a treatment effect on OS was 0.63. Median TTP was associated with median OS. The rs value between TTP and OS was 0.73 (95% confidence interval (CI) 0.40 – 0.89, p < 0.001) and the corresponding R2 was 0.42. Conclusions: Our study results suggest that TTP could be used as a surrogate marker for OS in the clinical trials of advanced HCC. However, the results suggest modest correlation between treatment effects on TTP and OS. Along with individual-level analysis more evidences are needed to confirm our finding.

Real-world experience of pembrolizumab plus lenvatinib in unresectable hepatocellular carcinoma in Taiwan.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16627-e16627 ◽  
Author(s):  
Chi-Jung Wu ◽  
Ya-Wen Hung ◽  
Pei_Chang Lee ◽  
ChiehJu Lee ◽  
Ming Huang Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Real World ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Objective Response ◽  
Post Treatment ◽  
Advanced Hcc ◽  
Unresectable Hepatocellular Carcinoma

e16627 Background: Multi-kinase inhibitors and immune checkpoint inhibitors (ICIs) are treatment options of systemic therapy for unresectable hepatocellular carcinoma (HCC). Targeted therapy can potentially enhance T cell infiltration and activation, consequently, cooperate with ICIs to produce synergistic anti-tumor effects. The ongoing clinical trial shows promising data by combining pembrolizumab with lenvatinib for advanced HCC. The study tried to evaluate the treatment response and adverse events of pembrolizumab plus lenvatinib for HCC in real-world setting. Methods: From Jul. 2019, patients who received pembrolizumab plus lenvatinib for unresectable HCC in a tertiary medical center in Taiwan were prospectively enrolled. The status of HCC was either in advanced HCC or failed by prior locoregional treatment. The dosage of pembrolizumab was 100mg every 3 weeks. The starting dose of lenvatinib was 10mg per day then titrating to weight-based dose according to recommendation. Patients who had received at least 2 cycles of pembrolizumab were evaluated in this report. The tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). The treatment related adverse events (TRAEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Till the end of Jan. 2020, 27 patients had received at least 2 cycles of pembrolizumab, and 17 had evaluable post-treatment images either by CT or MRI. There were 6 (22.2%) in BCLC B, and 21 (77.8%) in BCLC C. Of them, 17 (63%) were treated as the first-line systemic treatment, 8 as the second-line and 2 as the third line systemic treatment. Of the 17 cases with post-treatment image studies, there were 6 (35.3%) in partial response (PR), 7 (41.2%) in stable disease (SD), and 4 (23.5%) in progressive disease (PD) by RECIST v1.1; and 1 (5.8%) in complete response (CR), 9 (52.9%) in PR, 3 (17.6%) in SD and 4 (23.5%) in PD by mRECIST, respectively. The objective response rate (ORR) and disease control rate (DCR) by mRECIST were 58.7% and 76.5%, respectively. The most common TRAEs in any grade were hypertension 24 (88.4%), palmar-plantar syndrome 19 (70.4%), hypothyroidism 19(70.4%). The Grade 3/4 TRAEs were 3 (11.1%) with psoriasis-like skin reaction, 3 (11.1%) with hypertension and 2 (7.4%) with palmar-plantar syndrome. Conclusions: Pembrolizumab plus lenvatinib can produce excellent ORR and DCR with tolerable safety profiles. Such combination could be a promising strategy for unresectable HCC in the future.

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