Sep 15, 2021

Disclosures: Sangro reports receiving consulting fees from Adaptimmune, AstraZeneca, Bayer, Bristol Myers Squibb, BTG, Eisai, Exelixis, Eli-Lilly, IPSEN, Merck, Onxeo, Roche, Sirtex; receives lecture fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Eli-Lilly, Incyte, IPSEN, Roche, Sirtex and receives institutional research grants from Bristol Myers Squibb and Sirtex. ADD TOPIC TO EMAIL ALERTS Receive an email when new articles are posted on Please provide your email address to receive an email when new articles are posted on . Please try again later. If you continue to have this issue please contact customerservice@slackinc.com . Back to Healio Recently the European Association for the Study of the Liver updated its clinical practice guidelines for management of hepatocellular carcinoma. Healio Gastroenterology spoke with Bruno Sangro, MD, director of the liver unit at Clínica Universidad de Navarra, and professor of internal medicine at the University of Navarra School of Medicine, in Pamplona, about EASL’s latest update to the recommendations for systemic therapy of HCC . Bruno Sangro Healio: Why did EASL decide to update the recommendations for systemic therapy of HCC? Sangro: The recommendations that were in the last version of the guidelines were introduced before the IMbrave-150 clinical trial had reported results and so the recommendation was sorafenib [Nexavar; Bayer] or lenvatinib [Lenvima; Eisai] as first-line therapies, followed by regorafenib [Stivarga; Bayer], cabozantinib [Cabometyx/Cometriq; Exelixis] or ramucirumab [Cyramza; Eli Lilly] as per the corresponding clinical trial data. The introduction of atezolizumab [Tecentriq; Genentech] plus bevacizumab [Avastin; Genentech] made us understand that there was an urgent need for recommendation in this systemic therapy field. This has changed entirely the way we should do systemic therapy in HCC patients. Healio: Can you discuss EASL’s new recommendations for systemic treatment of HCC? Sangro: The most important advance has been the introduction of atezolizumab plus bevacizumab as the standard of care in most countries, once the regulatory agencies have approved this based on the results of the IMbrave-150 trial. This is the most important advance that has, in turn, introduced several changes in the way we treat patients with systemic therapy. Up to now, we had sorafenib or lenvatinib as the standard of care, and other tyrosine kinase inhibitors and the VEGFR2 inhibitor ramucirumab as second line therapies, with certain limitations such as alpha-fetoprotein levels for ramucirumab or tolerability to sorafenib for regorafenib. What the introduction of atezolizumab plus bevacizumab as the recommended first-line therapy means is that there is virtually no experience regarding the efficacy of any other treatment, a second-line therapy, after atezolizumab plus bevacizumab. We recommend that decisions in this second-line setting should be based on different factors. First, availability, because not all drugs are equally accessible in different countries. Second, the toxicity profile of each agent and the patient characteristics making some toxicity profiles more or less appealing for a given patient. And third, to consider that there is no hierarchy. There is no reason to understand that lenvatinib, or even cabozantinib, should not be considered at the same level as sorafenib. The concept of sorafenib prior to any second-line drug should not be maintained once atezolizumab plus bevacizumab is the first line. These are the two main statements in the guidelines. Atezolizumab plus bevacizumab is the recommended first-line systemic therapy. Second-line systemic therapy would be a TKI. Then it is important to understand the population that should be treated. It includes all patients with metastases, or vascular invasion, but also those patients with liver disease in whom the burden of disease is too large to be fit for therapies like chemoembolization or radioembolization. In addition, the specific contraindications for either atezolizumab or bevacizumab should be considered when making the decision to treat a patient with atezolizumab plus bevacizumab. This position paper tries to provide guidance for physicians who deal with HCC, telling them what the currently available scientific evidence is and how this supports the decision to start, the option to choose, and the different ways that one can make the best out of the therapy by identifying adverse events and treating them correctly or addressing the needs for special population. We've also covered the evidence supporting treatment in special populations, from patients with liver transplantation to patients in hemodialysis, with viral co-infections, etc., and guidance for those specific indications for physicians treating patients with HCC. Healio: Can you discuss the difference between first- and second-line therapies in HCC? Sangro: First-line therapy means the therapy that you should consider in any patient who is a candidate for systemic therapy. It’s atezolizumab and bevacizumab based on the reported overall survival benefit compared to sorafenib. Not sorafenib but not lenvatinib either because lenvatinib was only non-inferior to sorafenib. Therefore, sorafenib or lenvatinib should only be considered the first option when there is a contraindication to any of the components of the combination. You need to have a contraindication to any of the drugs to recommend a different therapy. Healio: Will there be a trial or trials that you know of assessing the role of systemic therapies in stages beyond the advanced stage HCC? Sangro: There are different phase 3 trials running in the intermediate stage, testing the combination of transarterial chemoembolization with immunotherapy based on PD-1, PD-L1 inhibitors, plus/minus bevacizumab. In the earliest stages, there are also trials testing immunotherapy alone or in combination with bevacizumab as adjuvant therapy after successful resection or percutaneous ablation, but we still don't have any information coming from those trials, those are ongoing trials.