scholarly journals Case Report: Complete Response of Primary Massive Hepatocellular Carcinoma to Anti-Programmed Death Ligand-1 Antibody Following Progression on Anti-Programmed Death-1 Antibody

2021 ◽  
Vol 12 ◽  
Author(s):  
Gang Liu ◽  
Wenxuan Zhou ◽  
Xiaoli Li ◽  
Lijie Guo ◽  
Tingting He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Complete Response ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Progression Of Disease ◽  
Antibody Immunotherapy ◽  
Programmed Death 1

Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs due to chronic liver disease, and it has a high mortality rate and limited treatment options. Immune checkpoint inhibitors have been successfully introduced and used in cancer therapy, among which inhibitors of programmed death ligand-1 (PD-L1) and its receptor programmed death-1 (PD-1) are commonly administered for HCC as combination therapy, including combined anti-angiogenic and immunotherapy combination therapy. We report a case of a primary massive HCC patient with portal hepatic vein tumor thrombus who had a good response to atezolizumab in combination with bevacizumab, following progression of disease on combined immunotherapy with pembrolizumab and lenvatinib. This case demonstrates for the first time that an HCC patient who is resistant to anti-PD-1 antibody immunotherapy can benefit from anti-PD-L1 antibody immunotherapy, providing a potentially promising strategy for the treatment of HCC.

scholarly journals The Efficacy and Safety of Programmed Death-1 and Programmed Death Ligand 1 Inhibitors for the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Shukang He ◽  
Weichao Jiang ◽  
Kai Fan ◽  
Xiaobei Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Group Treatment ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Programmed Death 1

BackgroundHepatocellular carcinoma (HCC) is often diagnosed at an advanced stage where only systemic treatment can be offered. The emergence of immune checkpoint inhibitors (ICIs) provides hope for the treatment of HCC. In this study, we performed a meta-analysis to provide evidence for the efficacy and safety of ICIs in the treatment of HCC.MethodsThe following databases and websites were searched: Embase, PubMed, Cochrane Library and ClinicalTrials.gov. The primary endpoints were response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).ResultsFinally, twelve studies were included in this meta-analysis. When the corresponding outcome indicators and their 95% confidence intervals (CIs) were pooled directly, the overall RR, DCR, PFS and OS were 0.17 (0.15-0.19, I2 = 56.2%, P=0.009), 0.58 (0.55-0.61, I2 = 75.9%, P<0.001), 3.27 months (2.99-3.55, I2 = 73.0%, P=0.001), 11.73 months (10.79-12.67, I2 = 90.3%, P<0.001). Compared to the control group, treatment with ICIs significantly improved RR, PFS and OS, the OR and HRs were 3.11 (2.17-4.44, P<0.001), 0.852 (0.745-0.974, P=0.019) and 0.790 (0.685-0.911, P=0.001), respectively. However, no significant improvement in DCR was found in ICIs treatment in this meta-analysis.ConclusionHCC patients would benefit from ICIs treatment, however, more studies are needed in the future to provide more useful evidence for the treatment of HCC by programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors.

Tubulitis in a patient treated with nivolumab: Case report and literature review

2018 ◽  
Vol 2 (2-3) ◽  
pp. 107-112
Author(s):  
Viral Vakil ◽  
Mark Birkenbach ◽  
Katti Woerner ◽  
Lihong Bu
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint Inhibitors ◽  
Kidney Biopsy ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Metastatic Urothelial Carcinoma ◽  
Programmed Death 1

Kidney injury associated with use of immune checkpoint inhibitors that target the programmed death-1 molecule commonly manifests as acute tubulointerstitial nephritis on kidney biopsy. We present a case of a 66-year-old man who developed acute kidney injury at 6 months after initiation of treatment with anti-programmed death-1 antibody, nivolumab, for treatment of metastatic urothelial carcinoma. A renal biopsy showed focal moderate-to-severe lymphocytic tubulitis with minimal interstitial inflammation. Programmed death ligand-1 immunopositivity was detected only in tubules exhibiting lymphocytic tubulitis. The patient’s renal function improved to baseline with conservative management consisting of discontinuation of nivolumab followed by prednisone treatment.

Advanced papillary thyroid carcinoma responding to nivolumab

2020 ◽  
pp. 107815522092996
Author(s):  
Miguel Michel Ocampo ◽  
Jaren Lerner ◽  
Shawnt Tosonian ◽  
Constantin A Dasanu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Case Report ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Second Line ◽  
Papillary Thyroid ◽  
Programmed Death ◽  
Programmed Death 1

Introduction Clinical indications of immune checkpoint inhibitors have expanded to a variety of malignancies. Approximately one in six patients with hepatocellular carcinoma respond to programmed death 1 inhibitors nivolumab and pembrolizumab. Case report We report herein a patient with synchronous metastatic hepatocellular carcinoma and advanced papillary thyroid carcinoma treated with nivolumab in the second-line therapy. Management and outcome: The hepatocellular carcinoma showed a durable response to the second-line agent nivolumab. Remarkably, the patient’s papillary thyroid carcinoma also responded to this programmed death 1 inhibitor. Discussion To our knowledge, this is the first case report showing the efficacy of nivolumab in the treatment of metastatic papillary thyroid carcinoma. Further studies with immune checkpoint inhibitors in papillary thyroid carcinoma seem warranted.

Transarterial chemoembolization enhances programmed death 1 and programmed death‐ligand 1 expression in hepatocellular carcinoma

2020 ◽  
Author(s):  
Ahmed Montasser ◽  
Aurélie Beaufrère ◽  
François Cauchy ◽  
Mohamed Bouattour ◽  
Olivier Soubrane ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model

2020 ◽  
Vol 12 ◽  
pp. 175883592092203
Author(s):  
Chiao-Fang Teng ◽  
Ting Wang ◽  
Tzu-Hua Wu ◽  
Jia-Hui Lin ◽  
Fu-Ying Shih ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Combination Therapy ◽  
Mouse Model ◽  
Tumor Cell ◽  
Tumor Volume ◽  
Tumor Cell Apoptosis ◽  
Programmed Death Ligand 1 ◽  
Dc Vaccine ◽  
Programmed Death

Background: Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite remarkable advances in treatment, high mortality in HCC patients remains a big challenge. To develop novel therapeutic strategies for HCC is thus urgently needed to improve patient survival. Dendritic cells (DC)-based vaccines can induce tumor-specific immunity and have emerged as a promising approach for treating HCC patients; however, its effectiveness needs to be improved. Recently, blockade of programmed death ligand 1 (PD-L1) immune checkpoint pathway has been shown to enhance anti-tumor immune responses and exhibited great potential in HCC therapy. Methods: In this study, we generated DC vaccine by pulsing the C57BL/6J mouse bone marrow-derived DC with mouse hepatoma Hep-55.1C cell lysate. We developed a therapeutic strategy combining DC vaccine and PD-L1 inhibitor for HCC and evaluated its efficacy in an orthotopic HCC mouse model in which Hep-55.1C cells were directly injected into left liver lobe of C57BL/6J mouse. Results: Compared with a control group of mice, groups of mice treated with DC vaccine or PD-L1 inhibitor had significantly improved overall survival, reduced tumor volume, and increased tumor cell apoptosis. Remarkably, combination treatment with DC vaccine and PD-L1 inhibitor led to considerably longer overall survival, smaller tumor volume, and higher tumor cell apoptosis of mice than either treatment alone in a dose-dependent manner through inducing a stronger anti-tumor cytotoxic T cell response. Conclusion: Our data suggested that combination therapy with DC vaccine and PD-L1 inhibitor might have great promise as a novel treatment strategy for HCC.

scholarly journals Biomarkers in Immunotherapy-Based Precision Treatments of Digestive System Tumors

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhu Zeng ◽  
Biao Yang ◽  
Zhengyin Liao
Keyword(s):  
Digestive System ◽  
Checkpoint Inhibitors ◽  
Circulating Tumor Dna ◽  
Gastrointestinal Malignancies ◽  
Programmed Death Ligand 1 ◽  
Multiple Tumor ◽  
Programmed Death ◽  
Potential Biomarker ◽  
Tumor Mutational Burden ◽  
Programmed Death 1

Immunotherapy, represented by immune checkpoint inhibitors (mainly referring to programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockades), derives durable remission and survival benefits for multiple tumor types including digestive system tumors [gastric cancer (GC), colorectal cancer (CRC), and hepatocellular carcinoma (HCC)], particularly those with metastatic or recurrent lesions. Even so, not all patients would respond well to anti-programmed death-1/programmed death-ligand 1 agents (anti-PD-1/PD-L1) in gastrointestinal malignancies, suggesting the need for biomarkers to identify the responders and non-responders, as well as to predict the clinical outcomes. PD-L1expression has increasingly emerged as a potential biomarker when predicting the immunotherapy-based efficacy; but regrettably, PD-L1 alone is not sufficient to differentiate patients. Other molecules, such as tumor mutational burden (TMB), microsatellite instability (MSI), and circulating tumor DNA (ctDNA) as well, are involved in further explorations. Overall, there are not still no perfect or well-established biomarkers in immunotherapy for digestive system tumors at present as a result of the inherent limitations, especially for HCC. Standardizing and harmonizing the assessments of existing biomarkers, and meanwhile, switching to other novel biomarkers are presumably wise and feasible.

scholarly journals Systemic Therapy for Hepatocellular Carcinoma: Latest Advances

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 412 ◽  
Author(s):  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Systemic Therapy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Phase Iii ◽  
Term Survival ◽  
Targeted Agent

Systemic therapy for hepatocellular carcinoma (HCC) has changed drastically since the introduction of the molecular targeted agent sorafenib in 2007. Although sorafenib expanded the treatment options for extrahepatic spread (EHS) and vascular invasion, making long-term survival of patients with advanced disease achievable to a certain extent, new molecular-targeted agents are being developed as alternatives to sorafenib due to shortcomings such as its low response rate and high toxicity. Every single one of the many drugs developed during the 10-year period from 2007 to 2016 was a failure. However, during the two-year period from 2017 through 2018, four drugs—regorafenib, lenvatinib, cabozantinib, and ramucirumab—emerged successfully from clinical trials in quick succession and became available for clinical use. The efficacy of combination therapy with transcatheter arterial chemoembolization (TACE) plus sorafenib was also first demonstrated in 2018. Recently, immune checkpoint inhibitors have been applied to HCC treatment and many phase III clinical trials are ongoing, not only on monotherapy with nivolumab, pembrolizumab, and tislelizumab, but also on combination therapy with checkpoint inhibitors, programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) antibody plus a molecular targeted agent (bevacizumab) or the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, tremelimumab. These combination therapies have shown higher response rates than PD-1/PD-L1 monotherapy alone, suggesting a synergistic effect by combination therapy in early phases; therefore, further results are eagerly awaited.

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