Clinical Oncology

[Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond]

MASATOSHI Kudo1

DECEMBER 30, 2019

Clinical Oncology - 2019;6(04)

[Systemic therapy for hepatocellular carcinoma (HCC) has markedly advanced since the survival benefi t of a molecular targeted agent, sorafenib, were demonstrated in the SHARP and Asia Pacifi c trials in 2007. Treatment options for patients with advanced HCC increased by sorafenib, and long-term survival for patients with advanced stage HCC has become possible to some extent. However, development of a more potent fi rst-line novel molecular targeted agent replacing sorafenib and a potent second-line agent after disease progression on or intolerant to sorafenib has been warranted because sorafenib lacks tumor shrinking/necrotizing effects and induces relatively severe adverse events such as hand foot skin reaction. Many agents in the 1st line and 2nd line setting were attempted to develop between 2007 and 2016, but all of these clinical trials failed. On the other hand, clinical trials of 4 agents (regorafenib, lenvatinib, cabozantinib, and ramucirumab) succeeded in succession in 2017 and 2018, and their use in clinical practice is possible (regorafenib and lenvatinib) or underway (cabozantinib and ramucirumab). Furthermore, all of 5 clinical trials of combination therapy with transcatheter chemoembolization (TACE) plus a molecular targeted agent failed to date, however, the combination of TACE and sorafenib (TACTICS trials) was reported to be successful and presented at ASCO in 2018. Phase 3 clinical trials of immune checkpoint inhibitors and a combination therapy of immune checkpoint inhibitors and molecular targeted agents are also ongoing, which suggests treatment paradigm of HCC in all stages from early, intermediate and advanced stage, is expected to be changed drastically in the very near future.]

AFFILIATIONS

  1. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan

COMMENTS

0 comments

Further articles in this publication

Clinical Oncology

[Treatment of cholangiocellular carcinoma]

ANDRÁS Csilla, ÁRKOSY Péter

[Tumors of the biliary tract are a rare entity, at the time of diagnosis most of the patients are in advanced stage and operation can’t be effectuated. After operation the risk of recurrence is high. The standard adjuvant therapy is capecitabin based on the results of BILCAP study. In advanced stage or in the presence of metastates the standard fi rst line treatment is gemcitabine and cisplatin therapy, there are noninferiority results from a Japan study with gemcitabin and S1 combination therapy. There was no evidence of second line treatment possibilities after gemcitabine and cisplatin therapy until 2019, but based on the results of ABC-06 study mFOLFOX could be the choice in the future. In the case of MSI-H/dMMR tumors immuntherapy should be considered. Personalised medicine with matched molecular targeted therapy is a new option. There are 2 new molecular targets, FGFR and IDH, the preliminary result are very promising.]

Clinical Oncology

[Systemic anticancer therapy in patients undergoing hemodialysis]

VÉGH Éva, LAKATOS Gábor, TOKODI Zsófia

[The number of cancer patients receiving regular dialysis treatment is increasing. These patients could benefi t similarly from the regular anticancer therapies. Data of the use of antineoplastic therapies in this vulnerable patient population mainly come from case reports and small case series. The lack of knowledge and lack of practical experiences in this patient group may lead to suboptimal cancer treatment. Defi ning the indication for antineoplastic treatment and choosing the appropriate drug is a challenging task and the patients’ prognosis and quality of life aspects should be evaluated carefully. The timing of anticancer treatment and the dialysis is also an important issue in this decision-making process. Close cooperation between the oncologists and nephrologists is essential in the proper antineoplastic treatment of the dialysed patients.]

Clinical Oncology

[Sequential therapy of metastatic renal cell carcinoma]

TORDAY László

[The incidence of renal carcinoma is on the rise in developed countries, with the tumor being among the 10 most common malignancies. However, the survival of patients with irresecable renal carcinoma has improved signifi cantly in recent years, mainly due to signifi cant advances in oncology treatment. The use of agents acting on the VEGF and mTOR signaling pathways is widespread and has become a standard clinical practice in fi rst and later line therapy. Recent clinical trials have provided many new drugs with new targets (cMET and AXL, FGFR, PD-1/PD-L1, CTLA-4) and combinations thereof, and have completely redrawn the treatment landscape of metastatic renal carcinoma and signifi cantly improved clinical results. This report reviews data on targeted drug therapy of renal cell carcinoma and discusses the therapeutic position of various drugs and combinations to our knowledge.]

Clinical Oncology

[Cell death]

KOPPER László, TÍMÁR József

[Cell proliferation and cell death (mainly apoptosis) have programs forming a network to maintain the functional integrity of the organism. Apoptosis has an external and internal units with ligands, signalling pathways and targets. Besides, some other participants (e.g. p53) are involved in the regulation of cell death. Although, apoptosis is a multitargeted process, there is no useful therapy, if it is needed, to correct accumulation of unwanted cells.]

Clinical Oncology

[Prevention and treatment of venous thromboembolism in cancer patients]

[Venous thromboembolism (VTE) is a common and severe complication of cancer. Deep vein thrombosis and pulmonary embolism are the second most common cause of death in cancer patients. Cancer, tumor-related factors as well as patient’s general condition and comorbidities are responsible for the increased risk of VTE. Chemotherapy is one of the most important risk factors for VTE, increasing incidence of VTE by 6.5-fold. In my paper, current guidelines for cancer VTE prevention and treatment are reviewed. Hospitalized patients with active tumor are at higher risk for VTE, and thrombosis prophylaxis is recommended in all cases. Extensive, routine prophylaxis for advanced cancer patients receiving chemotherapy is not recommended, but may be considered in high-risk ambulatory cancer patients (Khorana-score ≥ 3). Risk factors may change during the course of cancer disease, and the score should be continually reviewed and prophylactic treatment changed as necessary. LMWH is the recommended agent for both primary and secondary prophylaxis/treatment. Direct oral anticoagulants (DOACs) are knocking on our door, but results from further clinical trials are pending to determine their exact role.]

All articles in the issue

Related contents

Clinical Oncology

[Treatment of hepatocellular carcinoma - today]

VÉGH Éva, DEMETER Gyula, BODOKY György

[The hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death globally, and at the same time, it is the main event leading to death in cirrhotic patients. In the etiology of HCC, the non-alcoholic liver disease may be an important cause besides the viral cirrhosis. The HCC’s staging systems (Child-Pugh scores, Cancer of the Liver Italian Programme/CLIP, Barcelona Clinic Liver Cancer/ BCLC) play an important role in predicting the prognosis and determining the appropriate therapy. In Europe, the treatment strategy is based on the BCLC staging system. Screening of cirrhotic patient is also important because curative therapy is available only for the early-stage HCC. Several therapeutic options exist in the intermediate stage disease; among them the radiofrequency ablation (RFA), the transarterial chemoembolization (TACE) and the percutan ethanol injection (PEI) are most important. For the advanced disease, the only approved systemic therapy is sorafenib, which has been well-tolerated and yielded a substantially relative improvement in overall survival. For patient in end-stage disease with impaired liver function or a poor performance status, only supportive care is recommended.]

Clinical Oncology

[Tyrosine-kinase inhibitors and bisphosphonates in the treatment of metastases from renal cell carcinoma]

EDUARD Vrdoljak, TOMISLAV Omrčen

[Bone metastases (BMs) are common in patients with renal cell carcinoma (RCC) and approximately in 30% of patients with metastatic RCC (mRCC) will develop. Inhibition of vascular endothelial growth factor (VEGF) has been pursued as a therapeutic target in the treatment of metastatic clear cell RCC (mRCC). Tyrosine kinase inhibitors (TKIs), such as sunitinib, pazopanib, sorafenib, and axitinib, became the therapy of choice for patients with mRCC. Apart from the undisputed effi cacy of TKI in treatment of mRCC, the problem of metastatic bone disease still remains. There is evidence that the presence of BMs in m-RCC patients has a signifi cant and clinically-relevant negative impact on survival and potentially on the outcome of VEGF-targeted therapy. Also, common practice in the treatment of such patients is bonedirected therapy with BPs. Recent evidence shows a potentially synergistic effect on effi cacy but also a potential impact on increased toxicity of combining TKIs and BPs. This review highlights the importance of this subject and aims to facilitate further research and optimize the treatment of this important and common group of RCC patients.]

Clinical Oncology

[Treatment of hepatocellular carcinoma - an update]

DEMETER Gyula, VÉGH Éva

[Last time we have described about the modern treatment of hepatocellular carcinoma (HCC) in „Klinikai Onkológia” in 2014 (1) and a detailed guideline regarding epidemiology, treatment according to BCLC staging system has been published as well in a special edition in this year (2). Here, we discuss mainly the fi rst- and second line systemic treatment of HCC according to our experience and the new results of clinical trials. 203 patients were treated in our Department between 2010 and 2016. These results have been presented already on the MKOT conference in 2016. In this year we have started second line systemic therapy with regorafenib in 9 cases.]

Lege Artis Medicinae

[Treatment of hepatocellular carcinoma by liver transplantation: results in Hungary]

GÖRÖG Dénes, VÉGSŐ Gyula, DOROS Attila, GERLEI Zsuzsa, FEHÉRVÁRI Imre, NEMES Balázs, KÓBORI László

[INTRODUCTION - Hepatocellular carcinoma is an internationally accepted indication for liver transplantation in selected cases. The aim of this study was to present treatment results of patients diagnosed with hepatocellular carcinoma and put on the waiting list between 1995 and 2010. PATIENTS AND METHODS - Sixty patients were put on the waiting list, 23 of who died or became unfit for operation while waiting for transplantation. Liver transplantation was performed in 37 patients. Pathological examination revealed no tumour in 3 of the explanted livers, whereas incidentalomas were detected in 4 livers that were explanted because of cirrhosis. Thus, in total 38 patients were examined. RESULTS - Four patients died within 3 months of surgery because of arterial circulatory problems or graft dysfunction and 14 patients died thereafter, including seven whose tumour recurred. There was no recurrence of tumours in the early state among the 25 patients meeting the Milan criteria, and the overall 1-, 3-, and 5-year survival rates with an average follow-up period of 39 months were similar to those after transplantation because of viral cirrhosis: 72%, 72% and 67% vs. 78%, 71% and 67%, respectively. Survival rates after tumours beyond the Milan criteria were significantly lower (69%, 38%, 23%). CONCLUSION - Early-state (T1,T2) hepatocellular carcinoma that has developed following cirrhosis and is unsuitable for resection can be efficiently treated with liver transplantation, but our results do not support the use of transplantation for the treatment of tumours that do not fit the Milan criteria.]