Let’s imagine a scenario where we’re not talking about a single tumor, but this tumor is 7 cm with an additional node—either metastasis or a synchronic tumor because it’s difficult to tell if you don’t run molecular studies—in another segment of 2 cm. We have 2 nodules, 7 cm and 2 cm, surgery is not the ideal strategy, and we are in the intermediate setting. TACE [transarterial chemoembolization] has been a standard of care for the last 15 years, and there are trials testing drug combinations with no positive results. I’m remembering the study by [Masatoshi] Kudo, [MD,] presented with lenvatinib or others in intermediate HCC [hepatocellular carcinoma]. Dr Chan, in which circumstances might you consider these combinations? Or do you treat the patient with the conventional standard of care, and then depending on the progression of the disease, you make a decision?

We know the BCLC [Barcelona Clinic Liver Cancer] B stage of HCC is a heterogeneous disease. Some patients who a relatively small disease burden, they will benefit from the TACE alone. Patients with larger tumors, like as mentioned larger than 7 cm, or with a tumor number of more than 5, or sometimes we call it up-to-7 criteria, will have a higher chance of developing refractoriness to TACE, even though we can technically treat them with it. In the APPLE [Asia-Pacific Primary Liver Cancer Expert] consensus statement, we call these TACE unsuitable tumors. We don’t have high-level evidence for how to treat this type of patient with a larger disease burden. One proposal, as mentioned by Dr Llovet, is that we can add a TKI [tyrosine kinase inhibitor] to the treatment of these tumors. When you read the data and look at the clinical trials, we have some study on axitinib, and while the response rate is higher, the PFS [progression-free survival] slightly improved, the overall survival [OS] has not dramatically changed. So I don’t think this will be routine.

Now, industries and investigators are testing the addition of PD-1 or PD-1 combinations, like the EMERALD-1 study, and we need to wait for the data from this phase 3 clinical trial. In the study by Kudo, which I’m a part of, we asked if a single systemic therapy can benefit this type of high-burden BCLC stage B disease, like beyond the up-to-7 criteria. We showed that single-agent lenvatinib in this type of TACE unsuitable patients, large disease burden, have a better overall survival and PFS in a matched prospective cohort study. This is not a randomized study, it’s a matched cohort study. Also, those patients treated with lenvatinib had preservation of hepatic function during the course of treatment, while patients treated with TACE have a higher chance of developing deterioration of function in terms of ALBI [albumin-bilirubin] score and Child-Pugh score. This is still an open area, and we need more studies in the future to guide us.

 I would say that overall, for intermediate HCC, this means liver-only disease without metastasis and good performance status, the standard of care is locoregional therapies, TACE, and even in the United States, Y-90 [yttrium-90 radioembolization] is accepted as an alternative option. Adding systemic therapies is not indicated by guidelines. There are preliminary data that are appealing. There are several ongoing trials, the EMERALD-1 , the LEAP-012, and the CheckMate 74W. These trials are combining locoregional and systemic therapies, but at this point we cannot indicate these treatments in the management of intermediate HCC.

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Gastroenterology experts discuss whether there a is a role for systemic therapy for the management of intermediate HCC.

Is There a Role for Systemic Therapy for Patients With Intermediate HCC?

 We assume that the primary treatment for this patient is resection, but some centers might consider transarterial radioembolization Y-90 or even TACE [transarterial chemoembolization]. What’s your opinion about these treatments at this early stage?

 This patient has a very high risk of relapse after surgery, and neoadjuvant treatment is a good option for our patient. Between days on radioembolization, I prefer radioembolization because the lesion of our patient is often 7 cm and their response is 2 days, and this isn’t better. It’s important to offer neoadjuvant treatment. We select patients with response and the probability of a better genetic profile. It’s important to perform neoadjuvant therapy for this patient before surgery. We don’t have phase 3 trial data, but we’re moving on with neoadjuvant therapy and locoregional therapy before surgery.

Andrea Casadei Gardini, MD, and Stephen L. Chan, MD, examine the use of TACE and TARE-Y90 for the treatment of HCC.  

Role of TACE and TARE in the Treatment of HCC

® titled “Emerging Treatment Considerations in Hepatocellular Carcinoma: An Expert Case-Based Discussion.” I’m Josep Llovet, and I’m the director of the liver cancer program and a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York. I’m joined by 2 experts in the field of liver cancer. I’d like to welcome my esteemed fellow panelists. Dr Andrea Casadei, please introduce yourself.

 Thank you. My name is Andrea Casadei Gardini, and I’m an oncologist at San Raffaele Research Hospital in Milan, Italy. I’m the head of the liver unit in the oncology department.

 Thank you. I’m Steven Chan. I’m a professor in the department of clinical oncology at the Chinese University of Hong Kong, and I’m a medical oncologist.

 Thank you for joining me in this discussion about the emerging treatment in HCC [hepatocellular carcinoma]. We’re going to discuss several updates in HCC, including abstracts at ASCO [American Society of Clinical Oncology Annual Meeting] and ESMO [European Society for Medical Oncology Congress] 2021. We’ll also discuss the data of other updates in the treatment landscape and their impact on clinical practice. Let go to the first topic. Is there a role for adjuvant or neoadjuvant therapy in patients with HCC undergoing resection, or ambulatory treatment?

 I’m going to present a patient’s history briefly. We have a 72-year-old woman with a mild alcoholic cirrhosis. An abdominal ultrasound was performed because of an increased gamma GT. Subsequent CT demonstrated liver cancer with a single tumor of 7 cm. There are no vascular invasions or extrahepatic spread. The liver function is Child-Pugh class A, and the ECOG performance status was 0. The liver function, albumin, and the bilirubin were normal, and the alpha-fetoprotein was 20 ng/mL. This patient underwent surgery. The pathologies showed complete recession and confirmed it to be FCC [follicular cell carcinoma].

 This is framing a classic case in which resection is performed. R0 is achieved by the pathology assessment. The natural history of these patients would be 50% to 70%, with recurrent rate at 5 years. Do we have a choice in terms of primary adjuvant therapy? What do you think about the current data on therapies for this patient?

 This is an important area because in the West, and more likely in the East, our surgeons like to operate on patients with liver tumors, but the criteria for operation may be different. Western surgeons are more selective in terms of selecting the patient for surgery. In the East, our surgeons tend to operate on patients with advanced tumors, bigger tumors, multiferroics…this explains why the recurrence rate and the survival may vary between the East and West and even between different centers. Can we give atrophic treatment for these patients so that we can reduce the recurrences? In the old days, in our center, we participated in a study, adjuvant iodine-131, which showed no improvement in overall survival. In the era of sorafenib, there was the STORM phase 3 study. Unfortunately, the use of sorafenib was unable to prolong disease-free survival, and we found adjuvant use of TTI [time to treatment initiation] was not tolerable. A lot of patients opted for poor compliance. We’re moving toward the adjuvant use of anti–PD-1. Now we have a number of phase 3 trials by different industries, some testing on single use of anti PD-1, some on combinations.… We need data. The regimen works in the metastatic setting or advanced setting, but that doesn’t mean it must work in the adjuvant setting, when there’s no gross tumor. We don’t have a standard, but we eagerly await those phase 3 clinical trials.

 I concur. After running more than 20 phase 3 trials in this arena, all these trials were negative, except 1 with adoptive immunotherapy. This has not been adopted by guidelines. Unfortunately for this patient, at this point, the decision could be to follow the patient with a regular screening to check for potential recurrence and tag them early. There’s no recommended systemic therapy or operational therapy in the adjuvant setting. There are few studies already reported in the neoadjuvant. These studies are assessing checkpoint inhibitors in a small group of 20 patients. So far, the results are promising, with a readout of pathological response. We need a thorough phase 3 investigation so I could say that the neoadjuvant arena is appealing. It’s scientifically sound, and the preliminary data are promising, but we need additional studies.

Stephen L. Chan, MD, reviews the case of a 72-year-old woman with mild alcoholic cirrhosis and provides insight on the potential role of adjuvant and neoadjuvant therapy for the treatment of HCC.

Andrea Casadei Gardini, MD, San Raffaele Research Hospital

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Is There a Role for Systemic Therapy for Patients With Intermediate HCC?

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