Impact of Multi-Drug Sequential  Therapy on Survival in Patients with Unresectable Hepatocellular Carcinoma

Kudo, Masatoshi

doi:10.1159/000514194

Cited by 16 publications

(16 citation statements)

References 38 publications

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“…Additionally, atezolizumab–bevacizumab has shown to be not cost-effective as compared to sorafenib (Wang et al 2021 ), which will restrict its use, especially in resource-limited countries. Furthermore, sorafenib will remain an important second-line treatment option in patients who progressed after atezolizumab–bevacizumab (Kudo 2021 ), and optimized treatment decision-making needs to be supported. For example, the survival rate at 12 months of atezolizumab–bevacizumab-treated patients was 67.2% in the IMbrave150 study (Finn et al 2020 ), and patients with IL-6 or IL-8 values lower than cut-off values had similar rates of overall survival (66.6%) at the same time point in our study under sorafenib.…”

Section: Discussionmentioning

confidence: 99%

Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

Öcal

Schütte

Kupčinskas

et al. 2021

J Cancer Res Clin Oncol

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Purpose To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Methods A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. Results Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9–8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2–4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22–7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02–4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011). Conclusion IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.

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Section: Discussionmentioning

confidence: 99%

Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

Öcal

Schütte

Kupčinskas

et al. 2021

J Cancer Res Clin Oncol

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“…Exhausted cells also present high expression of inhibitory receptors such as Programmed Cell Death Protein 1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), Lymphocyte-activation gene 3 (LAG-3), CD160, B- and T-lymphocyte attenuator (BTLA), cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) ( Figure 2 ) [ 133 , 134 , 135 , 136 , 137 , 138 ]. Programmed Cell Death Ligand 1 (PD-L1) is a transmembrane protein expressed on the surface of certain cancer cells and is a co-inhibitory factor of the immune response.…”

Section: Factors Influencing T-cell Persistence In Clinical Settingsmentioning

confidence: 99%

Improving CAR T-Cell Persistence

Pietrobon

Todd

Goswami

et al. 2021

IJMS

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Over the last decade remarkable progress has been made in enhancing the efficacy of CAR T therapies. However, the clinical benefits are still limited, especially in solid tumors. Even in hematological settings, patients that respond to CAR T therapies remain at risk of relapsing due to several factors including poor T-cell expansion and lack of long-term persistence after adoptive transfer. This issue is even more evident in solid tumors, as the tumor microenvironment negatively influences the survival, infiltration, and activity of T-cells. Limited persistence remains a significant hindrance to the development of effective CAR T therapies due to several determinants, which are encountered from the cell manufacturing step and onwards. CAR design and ex vivo manipulation, including culture conditions, may play a pivotal role. Moreover, previous chemotherapy and lymphodepleting treatments may play a relevant role. In this review, the main causes for decreased persistence of CAR T-cells in patients will be discussed, focusing on the molecular mechanisms underlying T-cell exhaustion. The approaches taken so far to overcome these limitations and to create exhaustion-resistant T-cells will be described. We will also examine the knowledge gained from several key clinical trials and highlight the molecular mechanisms determining T-cell stemness, as promoting stemness may represent an attractive approach to improve T-cell therapies.

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“… 13 The liver function largely contributed to the clinical outcome of systemic therapies, including atezolizumab plus bevacizumab, 20 lenvatinib, 21 sorafenib, 22 and ramucirumab. 23 , 24 In addition, the liver function was also a predictive factor relevant to the transition of the postprogression treatment after sorafenib 25 and lenvatinib. 26 These previous reports indicated that a decreased albumin level and increased total bilirubin level were negative factors associated with the PFS and OS, which agreed with the present results.…”

Section: Discussionmentioning

confidence: 99%

The hepatocellular carcinoma modified Gustave Roussy Immune score (HCC‐GRIm score) as a novel prognostic score for patients treated with atezolizumab and bevacizumab: A multicenter retrospective analysis

et al. 2022

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Aim This study investigated whether or not the hepatocellular carcinoma modified Gustave Roussy Immune Score (HCC‐GRIm‐Score) serves as a prognostic indicator for HCC patients treated with atezolizumab and bevacizumab (Atez/Bev). Methods A total of 405 HCC patients who received Atez/Bev from September 2020 to January 2022 at 22 different institutions were included in this retrospective study. The HCC‐GRIm score was based on the combination of the albumin level (<3.5 g/L = 1 point), lactate dehydrogenase (≥245 U/L = 1 point), neutrophil‐to‐lymphocyte ratio (≥4.8 = 1 point), aspartate aminotransferase‐to‐alanine aminotransferase ratio (≥1.44 = 1 point), and total bilirubin level (≥1.3 mg/dl = 1 point). Patients were divided into the low‐score group (0, 1, or 2 points) and the high‐score group (3, 4, or 5 points). Results There were 89 (22.0%), 141 (34.8%), 106 (26.2%), 49 (12.1%), 16 (4.0%), and 4 (1.0%) patients with scores of 0, 1, 2, 3, 4, 5, respectively. The progression‐free survival (PFS) in the low‐score group was significantly longer than that in the high‐score group (median 7.8 vs. 3.5 months, p < 0.001). The median overall survival (OS) of the low‐score group was not reached at the time cutoff, with a 1‐year survival rate of 75.5%, whereas the median OS of the high‐score group was 8.5 months, showing a significant difference (p < 0.001). A high HCC‐GRIm score was a significant unfavorable factor associated with the PFS and OS in multivariate analyses (p = 0.002 and p < 0.001, respectively). Conclusions The HCC‐GRIm score serves as a novel prognostic score for HCC patients treated with Atez/Bev.

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Impact of Multi-Drug Sequential Therapy on Survival in Patients with Unresectable Hepatocellular Carcinoma

Cited by 16 publications

References 38 publications

Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

Improving CAR T-Cell Persistence

The hepatocellular carcinoma modified Gustave Roussy Immune score (HCC‐GRIm score) as a novel prognostic score for patients treated with atezolizumab and bevacizumab: A multicenter retrospective analysis

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