2020
DOI: 10.1016/j.jhep.2019.09.025
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Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma

Abstract: Immune checkpoint inhibitor (ICI) therapy targeting anti-programmed cell death-1 (anti-PD-1) or its ligand (anti-PD-L1) is the backbone of numerous combination regimens aimed at improving the objective response and survival of patients with hepatocellular carcinoma (HCC). Clinical trials of immunooncology regimens in other cancer types have shed light on issues of study design, including how to choose candidate regimens based on early-phase trial results, statistical considerations in trials with multiple prim… Show more

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Cited by 369 publications
(374 citation statements)
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References 156 publications
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“…Nivolumab and pembrolizumab gained approval for treatment of advanced HCC based on encouraging results from phase I/II studies in advanced HCC patients with objective response rates of 17%-20% [70,71] . However, results from two phase III clinical studies did not reveal statistically significant improvement in survival benefit [72,73] . There are several ongoing trials with monoclonal antibodies against PD-1, such as nivolumab, pembrolizumab, tislelizumab, and camrelizumab, in HCC patients, either as monotherapy or in combination with other treatments.…”
Section: Anti-pd-1 Antibody and Anti-pdl1 Antibodiesmentioning
confidence: 96%
See 1 more Smart Citation
“…Nivolumab and pembrolizumab gained approval for treatment of advanced HCC based on encouraging results from phase I/II studies in advanced HCC patients with objective response rates of 17%-20% [70,71] . However, results from two phase III clinical studies did not reveal statistically significant improvement in survival benefit [72,73] . There are several ongoing trials with monoclonal antibodies against PD-1, such as nivolumab, pembrolizumab, tislelizumab, and camrelizumab, in HCC patients, either as monotherapy or in combination with other treatments.…”
Section: Anti-pd-1 Antibody and Anti-pdl1 Antibodiesmentioning
confidence: 96%
“…As with other cancers, the combination regimens of nivolumab and ipilimumab led to grade 3-4 treatment-related adverse events occurring in 37.7% patients, which were more frequently observed with combination regimens than with single-agents, especially in patients who received higher dosages of ipilimumab. However, most of the adverse events were manageable with timely recognition, steroid treatment, and discontinuation of immunotherapy, with a very low rate of liver failure [73,85,86] .…”
Section: Anti-ctla-4 Antibodymentioning
confidence: 99%
“…78,79 Faivre et al summarise the scientific rationale behind this combination strategy and the promising data from early-phase trials of combination therapy for HCC, 77 while Cheng et al further elaborate on recent advances in the development of predictive biomarkers, and explore the immune-related antitumour mechanisms of multikinase inhibitors (independent of their anti-VEGFR effects). 80 They also discuss the challenges of further development of different immunotherapy-based combination therapies, including selection and prioritisation of regimens based on limited preclinical and clinical data, and evaluation and management of adverse events. 80,81 Curative treatments of intrahepatic cholangiocarcinoma iCCA is a highly lethal hepatobiliary neoplasm whose incidence is increasing.…”
Section: Tyrosine Kinase Inhibitors For Advanced Hepatocellular Carcimentioning
confidence: 99%
“…80 They also discuss the challenges of further development of different immunotherapy-based combination therapies, including selection and prioritisation of regimens based on limited preclinical and clinical data, and evaluation and management of adverse events. 80,81 Curative treatments of intrahepatic cholangiocarcinoma iCCA is a highly lethal hepatobiliary neoplasm whose incidence is increasing. This rare malignancy has recently received considerable clinical and investigative attention.…”
Section: Tyrosine Kinase Inhibitors For Advanced Hepatocellular Carcimentioning
confidence: 99%
“…And thus, the 5-year survival rate for HCC patients was found to be less than 12% (4). Although existing drugs such as sorafenib and immune checkpoint inhibitors could help improve patients' prognoses, the effect is still unsatisfactory (5). Therefore, more sensitive biomarkers are earnestly required for the early detection of HCC.…”
Section: Introductionmentioning
confidence: 99%