scholarly journals How Much Time Should Be Waited and What Are the Main Findings to Evaluate the Hepatocellular Carcinoma Response to Regorafenib? A Real-Life Experience

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Gustavo Hideki Kawanami ◽  
Leopoldo Katsuda ◽  
Thiara Barcelos Rocha ◽  
Fabio da Silva Yamashiro ◽  
Leonardo Pelafsky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Kinase Inhibitors ◽  
Life Experience ◽  
Real Life ◽  
Treatment Modalities ◽  
Screening Methods ◽  
Second Line ◽  
Imaging Findings ◽  
Sorafenib Treatment

Background. Hepatocellular carcinoma is a relevant cause of mortality worldwide, mainly among patients who have a prior liver disease. In spite of clear recommendations regarding surveillance and screening methods, most patients are still diagnosed only when they are no longer candidates to curative treatment modalities, while others do not achieve the goals of such treatments, thus increasing the need of anticancer drugs. Moreover, when cirrhotic patients begin to receive these drugs, many types of adverse events are seen as a reason to withdrawal, even when there are findings suggesting a good response to the treatment. Case Summary. This case report is about a cirrhotic patient who received many types of treatment, from surgery and chemoembolization during early stages to first- and second-line systemic therapy when the disease turned to be advanced. Since he had no signs of liver dysfunction and suffered tumor progression during sorafenib treatment, regorafenib was initiated. The main findings that make this case important are the adverse events after taking this second-line agent, which would certainly be considered unacceptable and would lead to the drug withdrawal. The reasons why regorafenib was maintained are explained based on clinical and imaging findings, showing how this decision led to an excellent response. Conclusions. The knowledge of the main adverse events described in the pilot clinical trials can avoid unnecessary withdrawal of regorafenib. In addition, some clinical and imaging findings can be deemed as predictors of good response to tyrosine kinase inhibitors.

scholarly journals Baseline and Early Predictors of Good Patient Candidates for Second-Line after Sorafenib Treatment in Unresectable Hepatocellular Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1256 ◽  
Author(s):  
Hitomi Takada ◽  
Masayuki Kurosaki ◽  
Kaoru Tsuchiya ◽  
Yasuyuki Komiyama ◽  
Jun Itakura ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Disease Progression ◽  
Kinase Inhibitors ◽  
Tumor Burden ◽  
Second Line ◽  
Inclusion Criteria ◽  
Sorafenib Treatment ◽  
Unresectable Hepatocellular Carcinoma ◽  
Early Predictors

Background: Recent advances in the development of tyrosine kinase inhibitors (TKIs) have enabled patients with unresectable hepatocellular carcinoma (HCC) to receive multiple TKIs in sequence. The aim of this study was to identify predictors of good candidates for second-line treatment after disease progression during sorafenib treatment. Methods: This is a retrospective cohort study of 190 consecutive HCC patients who were treated with sorafenib in our hospital. Three criteria of good candidates for second-line TKI at the time of disease progression during sorafenib treatment were defined as follows: criterion 1 was the same as the inclusion criteria of the regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE) study, criterion 2 was the inclusion criteria of the RESORCE study plus Child–Pugh score 5, and criterion 3 was the inclusion criteria of the RESORCE study plus albumin–bilirubin (ALBI) grade 1. Factors at baseline and at week 4 during sorafenib treatment were used to predict patients fulfilling each of these three criteria. Results: The distribution of patients was 29%, 13%, and 6% in criteria 1, 2, and 3, respectively. Significant factors for meeting criterion 1 was the combination of baseline albumin >3.7 g/dL (odds ratio (OR) 2.7) plus degree of decrease in albumin (Δalbumin) at week 4 <0.2 g/dL (OR 2.6), or the combination of baseline ALBI score <−2.33 (OR 2.5) and ΔALBI at week 4 <0.255 (OR 4.9). For criterion 2, the value of baseline albumin and ALBI score was identical to criterion 1; however, Δalbumin (<0.1 g/dL) and ΔALBI score (<0.19) became stricter. For criterion 3, the value of baseline albumin (>3.8 g/dL) and ALBI (<−2.55) became stricter, as did Δalbumin (<0.1 g/dL) and ΔALBI (<0.085). Furthermore, tumor burden (>11) was selected as an additional predictor (OR 5.4). Conclusion: Predictors to satisfy the RESORCE study inclusion criteria were as follows: preserved liver function at baseline, as reflected by albumin or ALBI score, and small deterioration of liver function early during sorafenib therapy, as reflected by Δalbumin or ΔALBI at week 4. Liver function at baseline and degree of change in liver function during sorafenib treatment need to be stricter for better outcomes of liver function with disease progression.

scholarly journals Real-Life Experience of Sorafenib Treatment for Hepatocellular Carcinoma in Korea: From GIDEON Data

2016 ◽  
Vol 48 (4) ◽  
pp. 1243-1252 ◽  
Author(s):  
Do Young Kim ◽  
Hye Jin Kim ◽  
Kwang-Hyub Han ◽  
Sang Young Han ◽  
Jeong Heo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Life Experience ◽  
Real Life ◽  
Sorafenib Treatment

Sorafenib for Advanced Hepatocellular Carcinoma: A Real-Life Experience

2018 ◽  
Vol 36 (5) ◽  
pp. 377-384 ◽  
Author(s):  
Larisse Longo ◽  
Laura Bainy Rodrigues de Freitas ◽  
Deivid Santos ◽  
Ivana Grivicich ◽  
Mário Reis Álvares-da-Silva
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Life Experience ◽  
Real Life ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Second Line Therapy ◽  
Advanced Hcc ◽  
Line Therapy

Introduction: Sorafenib (SOR) has proved to be effective in patients with advanced hepatocellular carcinoma (HCC), since overall survival was higher in phase III clinical trials; however, disease progression can occur. Objectives: The study aimed to describe real-life experience in advanced HCC treatment with SOR at a university hospital in Brazil and to estimate the number of patients with indication of second-line therapy. Methods: This is a retrospective study that included cases of HCC with prescription of SOR based on real-life practice between 2011 and 2016. Demographic, clinical, and laboratory data were collected. Results: From 572 patients with HCC, SOR was prescribed in 103 cases. From them, 62.1% were classified as Child-Pugh (CP)-A, 54.4% as Barcelona Clinic Liver Cancer (BCLC)-C, and 74 (71.8%) started treatment. Overall survival was 25.5 (95% CI 17.0–34.1) months and 1-year survival was greater in patients who received SOR than in non-treated (88.7 vs. 44.4%, p < 0.001). There was no difference in survival between BCLC-B and C (p = 0.405), as well as CP-A and B (p = 0.919). In 21.6% of the patients, a second-line therapy with regorafenib was indicated. Conclusion: In this real-life study, SOR significantly increased the survival rate by 1 year in patients with advanced HCC regardless of BCLC staging and CP score. Second-line therapy would be indicated in 21.6% of cases.

scholarly journals Sorafenib treatment by Child–Pugh score in Latin American patients with hepatocellular carcinoma

2020 ◽  
Vol 16 (31) ◽  
pp. 2511-2520
Author(s):  
Laura L de Guevara ◽  
Lucy Dagher ◽  
Vanessa MV Arruda ◽  
Keiko Nakajima ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Latin American ◽  
Treatment Option ◽  
Real World ◽  
Safety Profile ◽  
Treatment Duration ◽  
Sorafenib Treatment ◽  
Safety And Efficacy ◽  
Grade 3

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child–Pugh status. Results: Of 90 evaluable patients (37% Child–Pugh A, 46% Child–Pugh B and 3% Child–Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child–Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child–Pugh A (21% grade 3/4) and 46% with Child–Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child–Pugh A and B and is a treatment option for both groups.

scholarly journals Immunotherapy with Checkpoint Inhibitors for Hepatocellular Carcinoma: Where Are We Now?

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 578
Author(s):  
Francesco Tovoli ◽  
Stefania De Lorenzo ◽  
Franco Trevisani
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Real Life ◽  
Randomised Clinical Trial ◽  
Immune Mediated ◽  
Long Time ◽  
Tumour Escape ◽  
Programmed Death Protein 1

Immune checkpoint inhibitors (ICIs) are beginning to show promise in the clinical management of hepatocellular carcinoma (HCC). Most recently, the anti-programmed death protein-1 (PD-1) agent atezolizumab combined with bevacizumab demonstrated superiority to sorafenib in a Phase 3 randomised clinical trial in the frontline setting. Other ongoing trials of immunotherapy for HCC are exploring different drug combinations, such as a double checkpoint blockade with PD-1 and anti-Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agents or with tyrosine kinase inhibitors. Moreover, ICIs are being tested in the adjuvant and neoadjuvant settings trying to resolve long-time unmet needs in HCC. The results of the ongoing trials will be critical to understanding the extent of the therapeutic role of ICIs in the complex and multifaceted clinical scenario of HCC. Still, there are some critical points which need further attention to clarify the best use of ICIs in HCC patients. For instance, the actual eligibility rate of patients in the real-life scenario, the prompt identification and correct management of immune-mediated adverse events, the identification of biomarkers predicting response or resistance, and strategies to prevent the tumour escape from ICI effect.

scholarly journals Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Lai Wei ◽  
Derek Lee ◽  
Cheuk-Ting Law ◽  
Misty Shuo Zhang ◽  
Jialing Shen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Kinase Inhibitors ◽  
Standard Treatment ◽  
Advanced Hepatocellular Carcinoma ◽  
Library Screening ◽  
Sorafenib Treatment ◽  
Genome Wide ◽  
Phosphoglycerate Dehydrogenase

Abstract Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common. By using genome-wide CRISPR/Cas9 library screening, we identify phosphoglycerate dehydrogenase (PHGDH), the first committed enzyme in the serine synthesis pathway (SSP), as a critical driver for Sorafenib resistance. Sorafenib treatment activates SSP by inducing PHGDH expression. With RNAi knockdown and CRISPR/Cas9 knockout models, we show that inactivation of PHGDH paralyzes the SSP and reduce the production of αKG, serine, and NADPH. Concomitantly, inactivation of PHGDH elevates ROS level and induces HCC apoptosis upon Sorafenib treatment. More strikingly, treatment of PHGDH inhibitor NCT-503 works synergistically with Sorafenib to abolish HCC growth in vivo. Similar findings are also obtained in other FDA-approved tyrosine kinase inhibitors (TKIs), including Regorafenib or Lenvatinib. In summary, our results demonstrate that targeting PHGDH is an effective approach to overcome TKI drug resistance in HCC.

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