Dr. John Gordan discusses the newest evidence-based guideline update from ASCO on systemic therapy for advanced hepatocellular carcinoma (HCC). He shares the updated recommendations for first-, second-, and third-line therapy for patients with Child-Pugh Class A liver disease, guidance for patients with Child-Pugh Class B liver disease. Dr. Gordan also touches on the importance of this guideline for both clinicians and patients and the outstanding questions regarding treatment options for HCC. Read the full guideline, “Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update” at www.asco.org/gastrointestinal-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/gastrointestinal-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.02745   Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.  My name is Brittany Harvey, and today I'm interviewing Dr. John Gordon from the University of California, San Francisco, lead author on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update." Thank you for being here, Dr. Gordon. Dr. John Gordon: Of course, happy to be here. Brittany Harvey: Before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Gordon, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.   So, to jump into the content of this episode, first, Dr. Gordon, what prompted this update to the Systemic Therapy for Advanced Hepatocellular Carcinoma Guideline, which was last published in 2020?  Dr. John Gordon: So, both the initial guideline in 2020 and then the update now were driven by advances in the standard of care. The original 2020 guideline was actually held for a little bit so that we could incorporate the availability of atezolizumab plus bevacizumab, which just reported back and then received FDA approval during 2020. We were happy to be able to provide what was a very timely update to clinicians about being able to use that new regimen that had really changed the face of therapeutics for advanced HCC. The update was driven again by a shift in therapeutics, specifically it was the presence of much more evidence for the use of combination CTLA-4, PD-1 or PD-L1 immunotherapy strategies. The primary thing was the availability of durvalumab plus tremelimumab, which was studied in the so-called HIMALAYA phase III trial. The key shift in this guideline was being able to incorporate those data as a second first-line option. Furthermore, when the 2020 guideline was released, data were just becoming available about the combination of ipilimumab and nivolumab, and were not covered in any great detail. So we wanted to be able to be sure to incorporate both of those regimens, which we thought were quite significant in the current therapy for advanced HCC. Brittany Harvey: Appreciate you providing that background on the evidence informing both the original guideline and this update. Next, I'd like to review the key recommendations of this update. So, starting with, what is recommended for first-line therapy? Dr. John Gordon: The current recommendation in the first-line setting is to offer patients either atezolizumab plus bevacizumab, sometimes called atezo-bev or durvalumab plus tremelimumab. But, at this time, those two