Centering discussion on a patient with early/intermediate-stage HCC, expert panelists consider the roles of transplant, resection, and adjuvant therapy, respectively.
Tanios Bekaii-Saab, MD: Hello, and welcome to this OncLive® Peer Exchange titled, “Emerging Treatment Considerations in Hepatocellular Carcinoma, an Expert Case-based Discussion.” I am Tanios Bekaii-Saab. I'm a professor of medicine at the Mayo Clinic in Scottsdale, Arizona, and I am joined today by a panel of experts in the field of liver cancer. I would like to welcome my esteemed fellow panelists to introduce themselves starting with Dr El-Khoueiry.
Anthony El-Khoueiry, MD: Hi, I am Anthony El-Khoueiry, a medical oncologist at the University of Southern California in Los Angeles.
Tanios Bekaii-Saab, MD: Dr Gholam?
Pierre Gholam, MD: I am Pierre Gholam, I am a hepatologist and a transplant hepatologist at Case Western Reserve University School of Medicine, in Cleveland, Ohio.
Tanios Bekaii-Saab, MD: Dr Vogel?
Arndt Vogel, MD: I'm a hepatologist from Hannover in Germany.
Tanios Bekaii-Saab, MD: Dr Yarchoan?
Mark Yarchoan, MD: I'm a medical oncologist at Johns Hopkins, Baltimore, Maryland.
Tanios Bekaii-Saab, MD: As you can see, we have a fantastic panel with large expertise in this disease. Thank you all for joining me. Let's get started on our first topic, which is a case presented by Dr Vogel.
Arndt Vogel, MD: Thank you very much. The first case is an older woman, 69 years old. She had a medical history of alcohol-induced liver cirrhosis, lost weight before she presented in the hospital, and had, as expected, slightly elevated liver enzymes. When we diagnosed the tumor, she got a CT [computed tomography] scan and there was a single tumor identified with the size of 4.2 centimeters. There was no evidence of muscular infiltration or extrahepatic metastases. Within the work-up, there was an interest in the liver function; albumin and bilirubin were normal. According to the liver function test, she had a type 2 liver cirrhosis. IV-1 AFP [alpha-fetoprotein]was not significantly elevated, and she was in a good ECOG performance status; she didn’t have many signs of portal hypertension. Platelets were always almost normal. As you might expect with such a history, the treatment of choice for this patient was liver resection. She underwent liver resection within R0 [for cure or complete remission] resection, clean borders on pathology. Here we can start our discussion.
Tanios Bekaii-Saab, MD: They're interesting. The dilemma is, do we have evidence, or enough evidence, for considering any form of adjuvant therapy in this group of patients? How would you treat? Arndt, we'll start with you. How would you treat a patient like this in your practice? Would you consider adjuvant therapy versus observation?
Arndt Vogel, MD: One question we could ask is whether she would be a candidate for liver transplantation. With 69 years of age, I think she's still a candidate. She had liver cirrhosis despite a good liver function. Tumor was within Milan [Criteria], so even in Germany she would be a candidate for liver transplantation. This is something that would need to be discussed with the transplant team: whether even after R0 resection, she would be a candidate for liver transplantation. I think that should be discussed in the multidisciplinary tumor board. Coming back to your question, do we have any evidence for adjuvant therapy? The largest study that has been conducted was the STORM study, and was a negative study. The aim was to treat patients after resection or local ablation with sorafenib for up to 1 year. It was a clear negative study, there was no improvement in recurrence-free survival. As far as I know, the overall survival data has never been reported, but based on that we can conclude that most likely adjuvant treatment with TKIs [tyrosine kinase inhibitors] with phase 3 evidence is not justified at this time. Today, I would try to include her in a clinical trial but I would not treat her with adjuvant therapy outside of a clinical trial.
Tanios Bekaii-Saab, MD: Pierre, transplant?
Pierre Gholam, MD: Transplant has become an issue that's been closely scrutinized in the setting of potentially resectable HCC [hepatocellular carcinoma], especially in the United States in the past few years, primarily because there has been a perception backed by evidence that we are over transplanting patients who might be adequate candidates for resection. To this end, the United Network for Organ Sharing has implemented wait-time accruals to disincentivize patients and providers from prematurely pulling the trigger on transplant when resection might be an appropriate option. In this case, the decision was made appropriately. This is a patient who would do well with resection. The odds of recurrence of tumor in someone who has had a previous HCC diagnosed is flirting with about 60% at 5 years. The writing is on the wall in terms of the future of the patient, but in terms of the actual therapy at the time it was implemented, I think we would all agree that it was appropriate.
Arndt Vogel, MD: I can add to 1 point regarding liver transplantation. In Europe or Germany, we have the time on the waiting list of almost 2 years. We have a test of time, and within these 2 years, we can still decide whether we proceed with transplantation or not. It's not that we would go directly to transplantation.
Tanios Bekaii-Saab, MD: Time is our friend in the decision-making process. Anthony, any role for adjuvant therapy? What does the data tell us, and not to ask you to predict the future, but what's going on in looking at potential options?
Anthony El-Khoueiry, MD: I fully agree that the current data does not support doing any adjuvant treatment for resected liver cancer. We should mention briefly what is the ideal patient for resection, and that tends to vary from regions in the world. In the US, I'll hear my colleagues say they prefer to resect single lesions. Of course, we would not resect someone with grossly visible vascular invasion on scans, and we try to avoid resecting patients with multiple lesions because they have a higher risk of recurrence. Would you agree, Pierre, Mark?
Pierre Gholam, MD: Yeah, absolutely. Our Asian colleagues on the surgery side have pushed the envelope when it comes to resection, sometimes with great success, but generally accepted criteria for appropriateness of resection include absence of portal hypertension, which we can now diagnose both by cross-sectional imaging. If you see evidence of splenomegaly, abdominal varices, or esophageal varices, as well as new criteria that reflect clinically significant portal hypertension as outlined by the Baveno VII criteria, which include a high FibroScan score, typically over 25 kPA [kilopascal], and a low platelet count, typically less than 150,000. If you apply those, you can reasonably weed out any patients who might do poorly with surgery. As Anthony just pointed out, solitary lesions tend to do better. The more lesions you have, the more multilobar disease you have, and the more likely you are to have a greater risk of recurrence. I think that is a good summary.
Anthony El-Khoueiry, MD: You asked me about the future. I think there's much excitement—the same way that immunotherapy has made a difference in the treatment of advanced disease. Several of these agents, whether single agent or in combination, are being evaluated in the adjuvant setting. Without going through the specific studies and names, nivolumab is a single agent being evaluated; pembrolizumab, durvalumab single-agent versus durvalumab with bevacizumab; same with atezolizumab in combination with bevacizumab. Multiple adjuvant trials. One of the challenges is that the inclusion criteria varies between these trials. Some of them have focused on taking higher-risk patients and some have not. We'll have to look through all these data as they come out.
Tanios Bekaii-Saab, MD: Do we have any hints that there may be signals from early studies?
Anthony El-Khoueiry, MD: There are hints about immunotherapy being promising in earlier stages of disease. Mark will talk later about the neoadjuvant setting being more effective in a less exhausted microenvironment with earlier stages of disease. If we think that way, these trials are promising, but we will see.
Transcript edited for clarity.