scholarly journals Systemic therapy of advanced hepatocellular carcinoma

2020 ◽  
Author(s):  
Peter R Galle ◽  
Jean-François Dufour ◽  
Markus Peck-Radosavljevic ◽  
Jörg Trojan ◽  
Arndt Vogel
Keyword(s):  
Hepatocellular Carcinoma ◽  
Standard Of Care ◽  
Treatment Choice ◽  
Current Evidence ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Systemic Treatments ◽  
First Time ◽  
Systemic Therapies

For a decade, sorafenib remained the only approved first-line treatment and standard of care for advanced hepatocellular carcinoma. The treatment landscape has been evolving rapidly over the past 2 years with the approval of additional first-and second-line systemic treatments, most of which are targeted therapies. The expected approval of immunotherapies constitutes a paradigm shift: for the first time in years, a checkpoint inhibitor in combination with a VEGF antibody recently outperformed sorafenib with regards to efficacy. The wider availability of systemic therapies increases the chance for longer overall survival but raises new questions concerning the role of local options, treatment choice and sequential treatment. Following an expert discussion at the German Cancer Congress 2020 in Berlin, this article aims to summarize the current evidence on and experience of treatment choice and sequence in first- and second-line therapy.

scholarly journals The Role of Immunotherapy in a Tolerogenic Environment: Current and Future Perspectives for Hepatocellular Carcinoma

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1909
Author(s):  
Liliana Montella ◽  
Federica Sarno ◽  
Annamaria Ambrosino ◽  
Sergio Facchini ◽  
Maria D'Antò ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Special Focus ◽  
Advanced Hepatocellular Carcinoma ◽  
Future Perspectives ◽  
Immune Organ ◽  
Systemic Treatments ◽  
Healthy Liver

In contrast to several tumors whose prognoses are radically affected by novel immunotherapeutic approaches and/or targeted therapies, the outcomes of advanced hepatocellular carcinoma (HCC) remain poor. The underlying cirrhosis that is frequently associated with it complicates medical treatment and often determines survival. The landscape of HCC treatment had included sorafenib as the only drug available for ten years, until 2018, when lenvatinib was approved for treatment. The second-line systemic treatments available for hepatocellular carcinoma include regorafenib, cabozantinib, ramucirumab, and, more recently, immune checkpoint inhibitors. However, the median survival remains below 15 months. The results obtained in clinics should be interpreted whilst considering the peculiar role of the liver as an immune organ. A healthy liver microenvironment ordinarily experiences stimulation by gut-derived antigens. This setup elucidates the response to chronic inflammation and the altered balance between tolerance and immune response in HCC development. This paper provides an overview of the mechanisms involved in HCC pathogenesis, with a special focus on the immune implications, along with current and future clinical perspectives.

scholarly journals First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Giuseppe Cabibbo ◽  
Maria Reig ◽  
Ciro Celsa ◽  
Ferran Torres ◽  
Salvatore Battaglia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Simulation Model ◽  
Cancer Progression ◽  
Randomized Clinical Trials ◽  
Health Benefit ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
First Line ◽  
Systemic Treatments

<b><i>Introduction:</i></b> Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. <b><i>Methods:</i></b> A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Sequences starting with first-line ATEZO plus BEVA followed by 5 second-line treatments (sorafenib [SORA], lenvatinib [LENVA], regorafenib, cabozantinib, and ramucirumab) were compared. The probability of transition between states (initial treatment, cancer progression, and death) was derived from RCTs. Life-year gained (LYG) was the main outcome. Rates of severe adverse events (SAEs) (≥ grade 3) were calculated. The incremental safety-effectiveness ratio (ISER) was calculated as the difference in probability of SAEs divided by LYG between the 2 most effective sequences. <b><i>Results:</i></b> ATEZO plus BEVA followed by LENVA (median OS, 24 months) or SORA (median OS, 23 months) was the most effective sequence, producing a LYG of 0.50 and 0.42 year, respectively. ATEZO plus BEVA followed by SORA was the safest sequence (SAEs 63%). At a willingness-to-risk threshold of 10% of SAEs for LYG, ATEZO plus BEVA followed by second-line SORA was favored in 72% of cases, while at a threshold of 30% of SAEs for LYG, ATEZO plus BEVA followed by second-line LENVA was favored in 69% of cases. <b><i>Conclusion:</i></b> Our simulation model provides a strong rationale to support ongoing trials evaluating second-line tyrosine-kinase inhibitors after first-line ATEZO plus BEVA. Future evidence from ongoing RCTs and prospective real-world studies are needed to prove the net health benefit of sequential treatment options for advanced HCC.

scholarly journals Systematic literature review of trials assessing recommended systemic treatments in hepatocellular carcinoma

2021 ◽  
pp. HEP41
Author(s):  
Sarah Ronnebaum ◽  
Abdalla Aly ◽  
Dipen Patel ◽  
Fernando Benavente ◽  
Juan-David Rueda
Keyword(s):  
Hepatocellular Carcinoma ◽  
Literature Review ◽  
Randomized Trials ◽  
Severe Disease ◽  
Performance Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Systemic Treatments

Aim: To identify and evaluate the similarity of all trials assessing recommended treatments for advanced hepatocellular carcinoma. Materials & methods: Single arm and randomized trials from any phase and published any time up to February 2021 were systematically searched. Results: From 5677 records reviewed, 50 trials were included in the review, and 24 for assessed for similarity. In the first-line (1L) setting, several trials assessing sorafenib were noted for enrolling patients with more severe disease and/or performance status than other 1L trials; trials within the second-line (2L) setting were generally similar. Median survival was <2 years in all trial arms. Conclusions: Trials assessing recommended treatments are largely similar and appropriate for quantitative comparisons of several efficacy and safety outcomes.

Atezolizumab in advanced hepatocellular carcinoma: good things come to those who wait

Immunotherapy ◽  
2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Angela Dalia Ricci ◽  
Giovanni Brandi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Phase Iii ◽  
Medical Community ◽  
Advanced Hepatocellular Carcinoma ◽  
Novel Treatments ◽  
Treatment Naïve ◽  
The Impact

Advanced hepatocellular carcinoma (HCC) patients present poor prognosis. However, recent years have seen the advent of several novel treatments in this setting, where the role of immune checkpoint inhibitors has been investigated. Among these, the PD-L1 inhibitor atezolizumab in combination with bevacizumab has reported unprecedented results in treatment-naive patients with unresectable disease, with the recently published IMbrave150 Phase III trial showing the superiority of the combination over sorafenib monotherapy, and after having attended more than a decade of ‘stagnation’, the HCC medical community has a new standard of care. Herein, we examine the development and the impact of atezolizumab in advanced HCC, summarizing the mechanism of action, pharmacokinetics and recent evidence from Phase I to III clinical trials.

Systemic therapies in elderly patients with advanced hepatocellular carcinoma: do not forget metronomic capecitabine

2021 ◽  
Author(s):  
Zainul Abedin Kapacee ◽  
Mairéad G. McNamara ◽  
Nicola de Liguori Carino ◽  
Angela Lamarca ◽  
Juan W. Valle ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Elderly Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Systemic Therapies

scholarly journals Favorable response to second-line atezolizumab and bevacizumab following progression on nivolumab in advanced hepatocellular carcinoma

Medicine ◽  
2021 ◽  
Vol 100 (25) ◽  
pp. e26471
Author(s):  
Brandon Swed ◽  
Kara Ryan ◽  
Omar Gandarilla ◽  
Manish A. Shah ◽  
Gagandeep Brar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line

scholarly journals Management of patients with intermediate stage hepatocellular carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097084
Author(s):  
David Prince ◽  
Ken Liu ◽  
Weiqi Xu ◽  
Minjiang Chen ◽  
Jin-Yu Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Standard Of Care ◽  
Intermediate Stage ◽  
Tumor Burden ◽  
Current Standard ◽  
Current Management ◽  
Heterogenous Group ◽  
Patient Subgroups ◽  
Significant Health ◽  
Systemic Therapies

Hepatocellular carcinoma (HCC) causes a significant health burden globally and its impact is expected to increase in the coming years. Intermediate stage HCC, as defined by the Barcelona Clinic Liver Cancer (BCLC) system stage B, represents up to 30% of patients at diagnosis and encompasses a broad spectrum of tumor burden. Several attempts have been made to further subclassify this heterogenous group. The current standard of care recommended by BCLC for intermediate stage HCC patients is transarterial chemoembolization (TACE), with modest outcomes reported. While refinements have been made to TACE technique and patient selection, it remains non-curative. In the real-world setting, only 60% of patients with intermediate stage HCC receive TACE, with the remainder deviating to a range of other therapies that have shown promise in select patient subgroups. These include curative treatments (resection, ablation, and liver transplantation), radiotherapy (stereotactic and radioembolization), systemic therapies, and their combination. In this review, we summarize the classifications and current management for patients with intermediate stage HCC as well as highlight recent key developments in this space.

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