Systemic Therapy for Advanced Hepatocellular Carcinoma Guideline

An interview with Dr. John D. Gordan from the University of California, San Francisco, and Dr. Michal G. Rose from Yale Cancer Center and VA Connecticut Healthcare System on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline." This guideline addresses first-line and subsequent systemic therapy options for patients with unresectable hepatocellular carcinoma that is not amenable to local therapies. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines.

Transcript

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BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network. A collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org

My name is Brittany Harvey, and today I'm interviewing Dr. John D. Gordon from the University of California, San Francisco, and Dr. Michal G. Rose from Yale Cancer Center, and VA Connecticut Health Care System, co-chairs on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline." Thank you for being here Dr. Gordon and Dr. Rose.

DR. MICHAL G. ROSE: Thank you.

DR. JOHN D. GORDON: Thank you.

BRITTANY HARVEY: First, 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 full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Gordon, do you have any relevant disclosures that are related to this guideline topic?

DR. JOHN D. GORDON: I do not.

BRITTANY HARVEY: Thank you. And Dr. Rose, do you have any relevant disclosures that are related to this guideline topic?

DR. MICHAL G. ROSE: I do not, either.

BRITTANY HARVEY: OK, then thank you. Then Dr. Rose, can you first explain the general purpose and the scope of this guideline?

DR. MICHAL G. ROSE: Of course. Thank you for this opportunity. As people know, the incidence of liver cancer, hepatocellular carcinoma, is rising rapidly in the United States and worldwide. And although there are multiple local and potentially curable treatments for early stage disease, the medical oncologist does get involved when these fail or if the patient presents with metastatic disease. And over the last three years, or bit more than three years, we've gone from having only one agent for advanced disease, which is sorafenib, to having nine agents approved for either first or subsequent lines of treatment. So this has created a really good problem for medical oncologists, how to choose between these multiple options. So the purpose of our guideline is to help us select the best treatment for the individual patient based on the best current evidence.

BRITTANY HARVEY: Great. Then this guideline covers both first line and subsequent systemic therapy options for patients with advanced hepatocellular carcinoma. Dr. Gordon, what are the key recommendations for first line therapy?

DR. JOHN D. GORDON: Thanks, and it's also a great pleasure for me to be on this podcast and I appreciate the entire process of putting together this guideline. In the front line setting, a lot of what motivates the completion of this guideline is the approval of the first front line combination for advanced HCC, which is the combination of bevacizumab and atezolizumab. So this was approved based on a report in the New England Journal of Medicine back in May that specifically studied a first line population of patients with advanced HCC and relatively preserved liver function. And the key recommendation of this guideline is that the combination of atezolizumab and bevacizumab be adopted for patients that meet this description. Particular caution is recommended for patients who are at risk of specific side effects or adverse events with these agents.

So for patients receiving bevacizumab, there is a particular risk of bleeding complications and MI or other ischemic complications. And so for patients with a recent MI or with uncontrolled esophageal varices, we recommend either management of these or not using this combination. Similarly, there are a range of contraindications to use of PD1, PDL1 inhibitors, such as atezolizumab, including history of various autoimmune diseases. And so we do not recommend this combination for patients with those co-morbidities. For patients with either more advanced liver failure or the specific risks that I just outlined, we're recommending continuation when safe and appropriate, of what was the previous standard of care. Which is front line treatment with either the oral TKI lenvatinib or the oral TKI sorafenib.

BRITTANY HARVEY: Great. Thank you for that overview of the first line recommendations. And Dr. Rose, what are the recommendations for second line therapy?

DR. MICHAL G. ROSE: So our team had a harder time with second line recommendations. And mainly because there's a lack, currently, of published data on treatment outcomes in patients who've received atezolizumab plus bevacizumab front line or lenvatinib front line. So we debated a lot in our group, which was a very multidisciplinary and collaborative group. And we did agree that patients who are well enough to receive second line therapy, that is their Child-Pugh was still A, and they had a good performance status, they should be considered for sorafenib, oral lenvatinib, if they had received atezolizumab plus bevacizumab in the front line setting. But of course other options for the second line would be cabozantinib or regorafinib, are reasonable in the evidence based options.

In patients who received sorafenib oral lenvatinib front line, we also discussed that it was reasonable to treat them with atezo bev because we presume that these patients did not have access to that combination in the front line. Of course if they meet the criteria that John outlined in the discussion of front line treatment. In patients who received sorafenib or lenvatinib front line, of course that we have data on using other tyrosine kinase inhibitors, such as cabozantinib or regorafinib. We also have data on using ramucirumab in patients who have an alpha fetoprotein greater than 400. And those were the recommendations that we made.

The other discussion that we had in these guidelines was the use of the immune checkpoint inhibitors second line. And we made the recommendation that they should be considered for patients who received sorafenib or lenvatinib in the front line setting, especially if they have contraindications to the use of further tyrosine kinase inhibitors. Or if they could not tolerate tyrosine kinase inhibitors.

BRITTANY HARVEY: Got it. Thank you for reviewing those second line systemic therapy options. Then Dr. Gordon finally, what is the importance of this guideline and how will it impact clinical practice and affect patients with advanced hepatocellular carcinoma?

DR. JOHN D. GORDON: Thanks. And so I think this very much follows on Michal's initial introduction about the purpose of this guideline, which was to address the dramatic proliferation of approved agents for advanced HCC. And what we were attempting to do, and I think achieved to the best that the evidence would support, was provide some degree of guidance on how providers could select both their first line agent and then later lines of therapy to the extent that patients are able to receive it. We think that the availability of these multiple agents for HCC, as Michal alluded to, is really an embarrassment of riches and now we need to think about how to use them wisely.

And we hope that actually as these new combinations and just a greater set of options enter clinical practice, it will be possible to actually do some of the studies that would address the questions that right now remain unanswered around treatments sequencing and the like. I think that there remain some interesting questions in the management of HCC, both for patients with more impaired liver function and for patients at the threshold between localized HCC who are still candidates for local regional therapies such as TACE or selective internal radiotherapy, and requiring systemic therapy as the outcomes from systemic therapy are becoming more positive. But in aggregate we think that these guidelines now provide something of a sequence for the treatment of patients who do require systemic therapy and hopefully an outline for further development.

BRITTANY HARVEY: Great. Thanks. It sounds like this will be important for both practitioners, and patients. So I want to thank you both for joining me on the podcast today and for your leadership on the development of these guidelines, Dr. Rose and Dr. Gordon.

DR. MICHAL G. ROSE: Thank you. And thank you for the opportunity to discuss them.

DR. JOHN D. GORDON: Yeah, thanks as well. And thanks to the amazing team at ASCO and to the entire expert panel, which put in quite a bit of time over the several years that we developed this guideline as more and more data became available.

BRITTANY HARVEY: Great. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.