The last 5 years have witnessed relevant advances in the systemic treatment of hepatocellular carcinoma. New data have emerged since the development of the EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma in 2018. Drugs licensed in some countries now include 4 oral multi-tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 4 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, nivolumab and pembrolizumab in monotherapy). Prolonged survival in excess of 2 years can be expected in most patients with sensitive tumours and well-preserved liver function that renders them fit for sequential therapies. With different choices available in any given setting, the robustness of the evidence of efficacy and a correct matching of the safety profile of a given agent with patient characteristics and preferences are key in making sound therapeutic decisions. The recommendations in this document amend the previous EASL Clinical Practice Guidelines and aim to help clinicians provide the best possible care for patients today. In view of several ongoing and promising trials, further advances in systemic therapy of hepatocellular carcinoma are foreseen in the near future and these recommendations will have to be updated regularly.
Summary null null Background null China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2–3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma. null null null Methods null T...
Abstract Systemic treatment of hepatocellular carcinoma (HCC) has seen significant progress in recent years including the arrival of immunotherapy. While several large phase III trials have built the fundament for multi-line treatment, they have focused on a highly selected group of patients excluding potentially confounding comorbidities. As a result, high quality evidence for the systemic treatment of HCC patients with various comorbidities is missing. This review summarises the current knowle...
Background & aims Radiological progression patterns to first-line sorafenib have been associated with post-progression and overall survival in advanced hepatocellular carcinoma, but these associations remain unknown for therapies in second- and later-line settings. This post hoc analysis of REACH and REACH-2 examined outcomes by radiological progression patterns in the second-line setting of patients with advanced hepatocellular carcinoma treated with ramucirumab or placebo. Methods Patients wit...
#1Jordi Bruix(University of Barcelona)H-Index: 115
Design and execution of clinical trials use definitions and criteria to permit a homogeneous study development avoiding heterogeneous decisions by investigators at different sites. Ideally, definitions and decision making in clinical practice should mimic those implemented in trials, but this is not the case. Target population is narrowly defined in trials and the goal of them is the evaluation of activity and toxicity, and ultimately, the demonstration of a survival benefit. In practice, treate...
BACKGROUND Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). METHODS Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and r...
Abstract Background and Aims Immune-checkpoint inhibitors are effective in many advanced tumors. However, there is scarce information regarding the radiological response to these agents in hepatocellular carcinoma outside clinical trials. We aimed to describe the radiological response in a retrospective cohort of hepatocellular carcinoma patients treated with nivolumab and to analyze the radiological evolution according to tumor response at first posttreatment radiological assessment. Methods We...
Abstract Background and Aims PD-1 inhibitor treatment can cause hyperprogressive disease (HPD), but the incidence, outcome, and predictive factors of HPD are unknown in hepatocellular carcinoma (HCC) patients treated with PD-1 blockade. Here, we assessed existence and factors predictive of HPD in advanced HCC patients treated with nivolumab. Methods Advanced HCC patients treated with nivolumab (n=189) were enrolled. Occurrence of HPD was investigated using tumour growth dynamics based on tumour ...
267Background: Atezo + bev has been approved globally for pts with unresectable HCC who have not received prior systemic therapy, based on results from IMbrave150 (NCT03434379). At a median of 8.6 ...
Last. Jordi Bruix(University of Barcelona)H-Index: 115
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Local and regional therapies are recommended for patients with hepatocellular carcinoma (HCC) in very early (BCLC 0), early (BCLC A), and intermediate stages (BCLC B. However, in clinical practice the decision to select one of the available approaches has to take into account several parameters that go far beyond the general recommendations exposed in clinical practice guidelines. Adequate selection of candidates for each option with proven survival benefit is key to secure an optimal outcome in...
Last. Chiun Hsu(NTU: National Taiwan University)H-Index: 44
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Importance Most patients with hepatocellular carcinoma (HCC) are diagnosed with advanced disease not eligible for potentially curative therapies; therefore, new treatment options are needed. Combining nivolumab with ipilimumab may improve clinical outcomes compared with nivolumab monotherapy. Objective To assess efficacy and safety of nivolumab plus ipilimumab in patients with advanced HCC who were previously treated with sorafenib. Design, setting, and participants CheckMate 040 is a multicente...
We present a case of a male patient with advanced hepatocellular carcinoma who developed hepatic and dermatological immune-related adverse events during treatment with the immune checkpoint inhibitor nivolumab. We discuss relevant aspects regarding the management of immune-related hepatic adverse events, including the incidence and onset of the event, the requirement for immune-modulating medication, resuming of immunotherapy, and the association between the occurrence of immune-related adverse ...
Sorafenib and regorafenib, multikinase inhibitors (MKIs) used as standard chemotherapeutic agents for hepatocellular carcinoma (HCC), generate reactive oxygen species (ROS) during cancer treatment. Antioxidant supplements are becoming popular additions to our diet, particularly glutathione derivatives and mitochondrial-directed compounds. To address their possible interference during HCC chemotherapy, we analyzed the effect of common antioxidants using hepatoma cell lines and tumor spheroids. In...
Last. Maria Reig(University of Barcelona)H-Index: 33
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Abstract null null The landscape of hepatocellular carcinoma (HCC) has changed since the incorporation of sorafenib in 2007 as the first pharmacological treatment for HCC. The combination of atezolizumab plus bevacizumab is currently the first-line treatment for HCC patients, and there are several second-line options approved for patients who had received sorafenib as the first-line treatment. The advantage of having multiple options of pharmacological treatment for HCC patients is associated to...
