Icaritin, a Novel Small-Molecule Immune Modulator in HBV-Related Refractory Advanced Hepatocellular Carcinoma: Safety, Immune Response, Durable Survival and Potential Predictive Biomarkers

2019 ◽  
Author(s):  
Shu-kui Qin ◽  
Qing Li ◽  
Jianmin Xu ◽  
Jun Liang ◽  
Ying Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Small Molecule ◽  
Predictive Biomarkers ◽  
Advanced Hepatocellular Carcinoma ◽  
Immune Modulator

scholarly journals Systemic treatment of hepatocellular carcinoma: from sorafenib to combination therapies

2020 ◽  
Vol 7 (2) ◽  
pp. HEP20
Author(s):  
Christoph Roderburg ◽  
Burcin Özdirik ◽  
Alexander Wree ◽  
Münevver Demir ◽  
Frank Tacke
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Current Data ◽  
Advanced Hepatocellular Carcinoma ◽  
Combination Therapies ◽  
Current Standard

For almost a decade, systemic therapy of advanced hepatocellular carcinoma (HCC) was limited to the tyrosine kinase inhibitor (TKI) sorafenib. Different agents including checkpoint inhibitors, TKIs and anti-VEGFR antibodies demonstrated efficacy in treatment. For the first time, the combination of atezolizumab and bevacizumab, a first-line treatment that is superior to the current standard was identified, potentially changing the way we treat HCC. In this review, we summarize current data on systemic treatment of patients with advanced HCC, focusing on combination therapies comprising immune checkpoint inhibitors, TKIs and locoregional therapies. We elucidate findings from recent trials and discuss such challenges as the lack of predictive biomarkers for identification of subgroups that will benefit from novel treatment strategies.

358 Trial in progress: A pilot study of combined immune checkpoint inhibition in combination with ablative therapies in subjects with hepatocellular carcinoma (HCC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A383-A383
Author(s):  
Hailey Carroll ◽  
Umair Aleem ◽  
Pooja Varghese ◽  
Marie Galligan ◽  
Michèle Bourke ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint ◽  
Innate Immune System ◽  
Innate Immune ◽  
University Hospital ◽  
Advanced Hepatocellular Carcinoma ◽  
Ablative Therapies

BackgroundLocoregional therapies for hepatocellular carcinoma, such as transcatheter arterial chemoembolization (TACE) or ablation, can induce a peripheral anti-tumor immune response. This may be amplified by immune checkpoint inhibitors (ICI). Early and higher anti-CTLA4 dosing could potentially lead to better priming and a stronger immune response. Recent data has suggested that early (Day 1 only), increased doses of anti-CTLA4 therapy, was associated with encouraging clinical activity and a tolerable safety profile. This study will evaluate dual immune checkpoint, CTLA4 (tremelimumab, day 1-only dosing) and PD-L1 (durvalumab) blockade in combination with TACE in patients with advanced HCC. Intensive peripheral immune-monitoring and longitudinal on-treatment tumor biopsies will focus on the role of the innate immune system, particularly Natural Killer cells, in anti-tumor responses.MethodsPatients with HCC (Childs Pugh A/B7; Barcelona Clinic Liver Cancer Stage B/C; ECOG 0/1; sorafenib-naïve or experienced) are being enrolled in a pilot study (Study Number UCDCRC/19/01) of tremelimumab at 2 dose levels (DL1 and DL2) in combination with durvalumab and TACE until disease progression (per irRECIST). DL1: tremelimumab (75 mg q28 days for 4 doses) and durvalumab (1500 mg q28 days). DL2: tremelimumab (300 mg in a single dose on day 1) and durvalumab (1500 mg q28 days). Subtotal TACE will be performed during study week 6 with the dose-limiting toxicity (DLT) evaluation period encompassing the first 8 weeks of the study. Primary endpoint is 6-month progression-free survival with secondary efficacy endpoints being safety, tolerability and overall survival. Exploratory objectives will evaluate changes in immune parameters in the tumor and peripheral blood of patients undergoing anti-CTLA4 therapy pre- and post-RFA or TACE. A major focus will be on the role of the innate immune system, particularly Natural Killer cells, in anti-tumor responses. Patients will be enrolled and treated at St Vincent’s University Hospital in Dublin, Ireland. This study is currently open and actively recruiting.ResultsN/AConclusionsN/ATrial RegistrationEudraCT Number 2019-002767-98Ethics ApprovalSt Vincent’s University Hospital Research Ethics Committee Study Number UCDCRC/19/01.ReferencesDuffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol 2017;66(3):545–51.Lencioni R, Petruzzi P, Crocetti L. Chemoembolization of hepatocellular carcinoma. Semin Intervent Radiol 2013;30(1):3–11.Slovak R, Ludwig JM, Gettinger SN, Herbst RS, Kim HS. Immuno-thermal ablations – boosting the anticancer immune response.Mehta A, Oklu R, Sheth RA. Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response?Gastroenterol Res Pract2016; 2016:9251375.Ng J, Dai T. Radiation therapy and the abscopal effect: a concept comes of age. Ann Transl Med 2016;4(6):118.O’Brien MA, Power DG, Clover AJ, Bird B, Soden DM, Forde PF. Local tumour ablative therapies: opportunities for maximising immune engagement and activation. Biochim Biophys Acta2014; 1846(2):510–23.Kelley RK, Sangro B, Harris WP, Ikeda M, Okusaka T, Kang Y-K, et al. Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC). Journal of Clinical Oncology 2020;38(15_suppl):4508-.Mariniello A, Novello S, Scagliotti GV, Ramalingam SS. Double immune checkpoint blockade in advanced NSCLC. Crit Rev Oncol Hematol 2020;152:102980.

scholarly journals The Growing Skyline of Advanced Hepatocellular Carcinoma Treatment: A Review

2021 ◽  
Vol 14 (1) ◽  
pp. 43
Author(s):  
Francesca Matilde Schipilliti ◽  
Ingrid Garajová ◽  
Giulia Rovesti ◽  
Rita Balsano ◽  
Federico Piacentini ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Main Type ◽  
Predictive Biomarkers ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Immune Therapies ◽  
Definition Of ◽  
Effective Drugs

Hepatocellular carcinoma (HCC) is the main type of liver cancer. In the majority of cases, HCC is diagnosed at the advanced stage, leading to poor prognosis. In recent years, many efforts have been devoted to investigating potential new and more effective drugs and, indeed, the treatment armamentarium for advanced HCC has broadened tremendously, with targeted- and immune-therapies, and probably the combination of both, playing pivotal roles. Together with new established knowledge, many issues are emerging, with the role of neoadjuvant/adjuvant settings, the definition of the best transitioning time from loco-regional treatments to systemic therapy, the identification of potential predictive biomarkers, and radiomics being just some of the topics that will have to be further explored in the next future. Clearly, the current COVID-19 pandemic has influenced the management of HCC patients and some considerations about this topic will be elucidated.

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