scholarly journals Donafenib in Chinese patients with advanced hepatocellular carcinoma (HCC): Really a new standard of care, or should we change paradigm for drug development in HCC?

2021 ◽  
Vol 15 (2) ◽  
Author(s):  
Francesca Negri ◽  
Camillo Porta
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Development ◽  
Standard Of Care ◽  
Chinese Patients ◽  
Advanced Hepatocellular Carcinoma

Not available

A real-world study of camrelizumab in the treatment of hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16121-e16121
Author(s):  
Yong-Yi Zeng ◽  
Wu-hua Guo ◽  
Zhibo Zhang ◽  
Xi Shi ◽  
Yongjie Su ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Real World ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Chinese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase Ii Studies ◽  
Clinical Trial Information

e16121 Background: Programmed cell death protein‐1(PD-1) targeted immunotherapy is a promising treatment strategy for advanced hepatocellular carcinoma. Anti-PD-1 inhibitor camrelizumab showed antitumour activity in phase II studies of advanced hepatocellular carcinoma, with manageable toxicities. This study evaluates safety and efficacy of camrelizumab in patients with advanced hepatocellular carcinoma. Methods: This is a multicentre, real‐world trial done at thirty-three centres in Fujian Province, China. Eligible patients were aged 18 to 75 years was diagnosed by China Liver Cancer Staging(CNLC) 2019 clinical diagnostic criteria or with a histological or cytological diagnosis of advanced hepatocellular carcinoma, unresectable or had progressed on or were intolerant to previous systemic treatment, and had an Eastern Cooperative Oncology Group performance score of 0-1. Patients were received camrelizumab 200 mg intravenously every 2 weeks plus other treatments, such as molecular targeted drug, transcatheyer artetial chemoembolization, radiotherapy and chemotherapy. The primary endpoints were progression-free survival. Safety was analysed in all treated patients. Follow-up is ongoing. Results: Between Mar 12, 2020, and Dec 25, 2020, 63 patients were screened for eligibility, of whom 41 eligible patients received camrelizumab were recruited and among whom 15 received apatinib, 16 received lenvatinib, 2 received sorafenib and 1 received regorafenib. Median followup was 5.28 months (IQR 1.63–10.20). Objective response was reported in 12 (29.3%; 95% CI 16.1–45.5) of 41 patients. Disease control was reported in 34 (82.9%; 95% CI 67.9–92.8) of 41 patients. The median PFS was not reached, and expected more than 9 months. Grade 3 or 4 treatment-related adverse events occurred in 21 (51.2%) of 41 patients; the most common were increased gamma-glutamyltransferase (15 [36.6%]) and increased aspartate aminotransferase (7 [17%]). One death was judged by the investigators to be potentially treatment-related (due to upper gastrointestinal bleeding). Conclusions: Camrelizumab showed promising efficacy and safety in pretreated Chinese patients with advanced hepatocellular carcinoma, and might represent a new treatment option for these patients. Clinical trial information: ChiCTR2000041405. Research Sponsor: Jiangsu Hengrui Medicine Co., Ltd. Clinical trial information: ChiCTR2000041405.

scholarly journals ANGPT2 and NOS3 Polymorphisms and Clinical Outcome in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1023 ◽  
Author(s):  
Giorgia Marisi ◽  
Elisabetta Petracci ◽  
Francesco Raimondi ◽  
Luca Faloppi ◽  
Francesco Giuseppe Foschi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Direct Sequencing ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Advanced Hepatocellular Carcinoma ◽  
Nucleotide Polymorphisms ◽  
Number Of Patients ◽  
Angiopoietin 2 ◽  
Oxide Synthase

Sorafenib represents the standard of care for advanced hepatocellular carcinoma (HCC), even though a large number of patients have reported limited efficacy. The aim of the present study was to evaluate the prognostic value of single-nucleotide polymorphisms on angiopoietin-2 (ANGPT2) and endothelial-derived nitric oxide synthase (NOS3) genes in 135 patients with advanced HCC receiving sorafenib. Eight ANGPT2 polymorphisms were analyzed by direct sequencing in relation to overall survival (OS) and progression-free survival (PFS). In univariate analysis, ANGPT2rs55633437 and NOS3 rs2070744 were associated with OS and PFS. In particular, patients with ANGPT2rs55633437 TT/GT genotypes had significantly lower median OS (4.66 vs. 15.5 months, hazard ratio (HR) 4.86, 95% CI 2.73–8.67, p < 0.001) and PFS (1.58 vs. 6.27 months, HR 4.79, 95% CI 2.73–8.35, p < 0.001) than those homozygous for the G allele. Moreover, patients with NOS3 rs2070744 TC/CC genotypes had significantly higher median OS (15.6 vs. 9.1 months, HR 0.65, 95% CI 0.44–0.97; p = 0.036) and PFS (7.03 vs. 3.5 months, HR 0.43, 95% CI 0.30–0.63; p < 0.001) than patients homozygous for the T allele. Multivariate analysis confirmed these polymorphisms as independent prognostic factors. Our results suggest that ANGPT2rs55633437 and NOS3 rs2070744 polymorphisms could identify a subset of HCC patients more resistant to sorafenib.

scholarly journals Sorafenib treatment on Chinese patients with advanced hepatocellular carcinoma

Medicine ◽  
2019 ◽  
Vol 98 (44) ◽  
pp. e17692 ◽  
Author(s):  
Shou-Wu Lee ◽  
Teng-Yu Lee ◽  
Yen-Chun Peng ◽  
Sheng-Shun Yang ◽  
Hong-Zen Yeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chinese Patients ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment

scholarly journals Organ Specific Responses to First-line Lenvatinib Plus Anti-PD-1 Antibodies in Patients With Unresectable Hepatocellular Carcinoma: a Retrospective Analysis

2021 ◽  
Author(s):  
Cheng Huang ◽  
Xiao-Dong Zhu ◽  
Ying-Hao Shen ◽  
Dong Wu ◽  
Yuan Ji ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Analysis ◽  
Surgical Resection ◽  
Chinese Patients ◽  
Specific Response ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Advanced Hcc ◽  
Overall Response ◽  
Organ Specific

Abstract BackgroundWe evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC).MethodsThis retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR).ResultsIn total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7-12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor.ConclusionsFirst-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.

scholarly journals Immunotherapy for advanced hepatocellular carcinoma: a focus on special subgroups

Gut ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 204-214 ◽  
Author(s):  
Matthias Pinter ◽  
Bernhard Scheiner ◽  
Markus Peck-Radosavljevic
Keyword(s):  
Hepatocellular Carcinoma ◽  
Solid Organ Transplantation ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
The United States ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Solid Organ ◽  
United States Food ◽  
Phase Iii Trials

Following the success of immune checkpoint blockers (ICBs) in different cancer types, a large number of studies are currently investigating ICBs in patients with hepatocellular carcinoma (HCC), alone or in combination with other treatments. Both nivolumab and pembrolizumab, as well as the combination of nivolumab plus ipilimumab have been granted accelerated approval by the United States Food and Drug Administration for sorafenib-pretreated patients. While nivolumab and pembrolizumab both failed to meet their primary endpoints in phase III trials, the combination of atezolizumab plus bevacizumab eventually improved overall and progression-free survival compared with sorafenib in a front-line phase III trial, and thus, will become the new standard of care in this setting. Despite this breakthrough, there are patient populations with certain underlying conditions that may not be ideal candidates for this new treatment either due to safety concerns or potential lack of efficacy. In this review, we discuss the safety of ICBs in patients with pre-existing autoimmune disease, IBD or a history of solid organ transplantation. Moreover, we summarise emerging preclinical and clinical data suggesting that ICBs may be less efficacious in patients with underlying non-alcoholic steatohepatitis or HCCs with activated Wnt/β-catenin signalling.

Response of advanced HCC to pembrolizumab and lenvatinib combination therapy despite monotherapy failure

2020 ◽  
Vol 58 (08) ◽  
pp. 773-777 ◽  
Author(s):  
Nadine Schulte ◽  
Moying Li ◽  
Tianzuo Zhan ◽  
Lena Dreikhausen ◽  
Janina Sollors ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The World ◽  
Vegf Inhibition ◽  
Tki Treatment

AbstractIn recent years, immune checkpoint inhibitors (ICIs) were successfully introduced to cancer therapy, and these drugs have already become essential for the treatment of various noncurable tumors. However, monotherapy in advanced hepatocellular carcinoma (aHCC) failed to show statistically significant improvement.Recently, the combination of atezolizumab and bevacizumab demonstrated efficacy of combining ICI and VEGF inhibition, further substantiating previous data on synergistic mechanisms among respective substance classes.As TKI treatment is currently standard of care for aHCC, and ICIs are approved by the FDA and available in many areas of the world, numerous patients may have been treated with monotherapy of those drugs. However, it remains unclear if failure to monotherapy has an impact on combination therapy. We therefore report a patient well responding to combination therapy despite previous failures to TKI and ICI monotherapy.

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