Current and future perspective on targeted agents and immunotherapies in hepatocellular carcinoma.

Published on Mar 1, 2021in Minerva gastroenterologica e dietologica3.072
· DOI :10.23736/S2724-5985.20.02775-0
Francesco Paolo Russo31
Estimated H-index: 31
(UNIPD: University of Padua),
Marco Senzolo40
Estimated H-index: 40
(UNIPD: University of Padua)
Sources
Abstract
Hepatocellular carcinoma (HCC) represents the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide. HCC occurs predominantly in patients with underlying chronic liver disease and cirrhosis, and it presents a poor prognosis in advanced stage. Since its approval, for the following 10 years, sorafenib remained the only systemic agent with proven clinical efficacy for patients with advanced HCC. Recently, more drugs have been studied and several advances in first‑line and second‑line treatment options should yield significant improvements in survival. Lenvatinib, another tyrosine‑kinase inhibitor, was found to be non-inferior to sorafenib in terms of overall survival (OS), with significantly better progression-free survival and objective response rate (ORR). The tyrosinekinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second‑line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second‑line setting among patients with AFP≥400 ng/dL. Moreover, good efficacy was seen in phase I/II trials of immune checkpoint inhibitors as monotherapy. Ongoing trials are evaluating combination immune checkpoint inhibitor and tyrosine‑kinase inhibitors or VEGF inhibitors for increasing overall survival in this patient population with advanced HCC.
References42
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#1Masatoshi Kudo (Kindai University)H-Index: 119
#2Kazuomi Ueshima (Kindai University)H-Index: 31
Last. Yasuaki AraiH-Index: 31
view all 27 authors...
Objective This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE. Design Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2–3 weeks before TACE, followed by 800 mg once daily during on-d...
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#1Robin Kate Kelley (UCSF: University of California, San Francisco)H-Index: 44
#2P. Mollon (Ipsen)H-Index: 3
Last. Ghassan K. Abou-Alfa (Cornell University)H-Index: 55
view all 10 authors...
: Cabozantinib and regorafenib are treatments approved for some patients with advanced hepatocellular carcinoma (HCC), a type of liver cancer, after disease progression despite prior sorafenib treatment. Cabozantinib, regorafenib and sorafenib are tyrosine kinase inhibitors (TKIs), meaning that they slow cancer progression by targeting specific ways that tumors grow. Cabozantinib and regorafenib offer benefits to patients compared with placebo (i.e., no treatment) for those who have progressed d...
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#1Bruno Sangro (University of Navarra)H-Index: 80
#2Stephen L. Chan (CUHK: The Chinese University of Hong Kong)H-Index: 61
Last. Peter R. GalleH-Index: 3
view all 6 authors...
Summary Immune checkpoint inhibitors (ICIs) have reshaped cancer therapy. ICIs enhance T cell activation through various mechanisms and may help reverse the exhausted phenotype of tumour-infiltrating lymphocytes. However, disrupting the key role that checkpoint molecules play in immune homeostasis may result in autoimmune complications. A broad range of immune-related adverse events (irAEs) involve almost every organ but mostly affect the skin, digestive system, lung, endocrine glands, nervous s...
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ABSTRACT Background Symptoms of advanced hepatocellular carcinoma (HCC) represent a substantial burden for the patient and are important endpoints to assess when evaluating treatment. Patient-reported outcomes were evaluated in subjects with advanced HCC and baseline alpha-fetoprotein (AFP) ≥400 ng/mL treated with second-line ramucirumab. Patients and methods Patients with AFP≥400 ng/mL enrolled in the REACH or REACH-2 phase 3 studies were used in this analysis. Eligible patients had advanced HC...
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Abstract Background SOR is approved as 1L therapy for pts with aHCC, but there is still an unmet need to prolong survival and improve tolerability. This phase III study compared clinical efficacy and safety of NIVO with SOR as 1L therapy in pts with aHCC. Methods Systemic therapy–naive pts aged ≥18 years with aHCC were randomized 1:1 to NIVO (240mg IV Q2W) or SOR (400mg oral BID). Primary endpoint was overall survival (OS). Additional endpoints were objective response rate (ORR) and progression-...
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#1Josep M. Llovet (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 123
#2K.V. Shepard (Eisai)H-Index: 1
Last. Andrew X. Zhu (Harvard University)H-Index: 101
view all 20 authors...
Abstract Background LEN is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT. PEMBRO is an anti-PD-1 monoclonal antibody. LEN monotherapy is approved for first-line treatment of uHCC. PEMBRO monotherapy has shown significant efficacy in the second-line treatment of HCC. We report updated results from a phase 1b trial of LEN + PEMBRO in uHCC. Methods In this open-label, phase 1b study of LEN + PEMBRO in uHCC, 104 patients (pts) with BCLC stage B (not amenable for transarterial ...
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#2Heinz-Josef Klümpen (UvA: University of Amsterdam)H-Index: 23
Abstract Background Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of a combination of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres and sorafenib with those of sorafenib alone in patients with advanced HCC. Methods SORAMIC is a randomised controlled trial comprising diagnostic, local ablation and palliative cohorts. Based on diagnostic study results patients were assi...
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#1Masatoshi Kudo (Kindai University)H-Index: 119
#2Kazuomi Ueshima (Kindai University)H-Index: 31
Last. Naoshi NishidaH-Index: 41
view all 20 authors...
Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate...
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#1Min-Ke He (SYSU: Sun Yat-sen University)H-Index: 6
#2Qi-Jiong Li (SYSU: Sun Yat-sen University)H-Index: 9
Last. Ming Shi (SYSU: Sun Yat-sen University)H-Index: 29
view all 17 authors...
Importance Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study. Objective To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasio...
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#1Dominik Bettinger (University of Freiburg)H-Index: 20
#2David J. Pinato (Imperial College London)H-Index: 30
Last. Eleni GkikaH-Index: 12
view all 27 authors...
Background and Aims: Stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment for patients with hepatocellular carcinoma (HCC), but its role in patients with advanced HCC is not yet defined. In this study, we aim to assess the efficacy and safety of SBRT in comparison to sorafenib treatment in patients with advanced HCC. Methods: We included 901 patients treated with sorafenib at six tertiary centers in Europe and Asia and 122 patients treated with SBRT from 13 ce...
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