Targeting Cancer With Tyrosine Kinase Inhibition in Frontline HCC
During a live virtual event, Daneng Li, MD, discussed the case of a 77-year-old woman with stage IV hepatocellular cancer and a Child-Pugh score of A. This is the first of 2 articles from this event.
A 77-year-old White woman presented to her primary care physician complaining of abdominal pain and fatigue. She had a history of cirrhosis due to heavy alcohol use; Crohn disease, controlled with infliximab [Avsola]; and a history of variceal bleeding, with banding 2 months ago. Her ECOG performance status was 1. A CT scan of her chest, abdomen, and pelvis with triphasic liver evaluation showed a 4.5-cm Liver Imaging Reporting and Data System 5 hepatic mass in the right lobe plus metastatic disease in the lung. She had a Child-Pugh score of A and an αfetoprotein level of 380 ng/mL. A biopsy was obtained and confirmed the diagnosis of hepatocellular carcinoma.
Which frontline therapy are you most likely to recommend for this kind of patient?
SAM S. YEH, MD: I’d chose lenvatinib [Lenvima] because the patient [is receiving infliximab]. Otherwise, I probably would have used atezolizumab [Tecentriq] plus bevacizumab [Avastin].
DANENG LI, MD: Anyone from the atezolizumab plus bevacizumab crowd? Why did you choose [that treatment]?
ARATI CHAND, MD: I think it is the most preferred option. In this patient, there [was all that] plausible bleeding and Crohn disease, but it looks like everything is well controlled. The patient was banded recently and the risk of bleeding is lower, and it looks like the Crohn is well controlled too. It is not very clear, but I am assuming it is well controlled with infliximab. So the patient isn’t going to get a flare. One could use immunotherapy if they had colitis and didn’t respond to steroids, but you could use infliximab in those patients anyway. I feel like that patient is already on treatment and the autoimmune disorder is well controlled. If this patient doesn’t have a severe form of Crohn disease that is uncontrolled, immunotherapy is still an option.
LI: These are all questions that face us in the real-world practice because if you look at the trials of atezolizumab plus bevacizumab, they definitely excluded patients who had significant autoimmune diseases, or they had to have lower than physiologic doses of prednisone to be eligible for the study. So there were very fixed criteria for patients excluded from the trial. In real-world practice, how many people are using atezolizumab plus bevacizumab for patients with autoimmune conditions?
CHAND: Well controlled is when the specialist treating the patient says it’s well controlled. I am not a gastroenterologist, and I wouldn’t comment if somebody’s Crohn disease is well controlled, and the same with other autoimmune diseases. It should come from the subspecialists treating the patient. Also, symptom-wise, what kind of symptoms does the patient have? If they are symptomatic, obviously, they are not well controlled.
MERIN STEPHEN, MD: I usually try to steer clear of immunotherapy when somebody is using an immunosuppressant if there is another option. I think there are active trials looking at these immunotherapies to see if they are acceptable in autoimmune diseases. Until we have more data, if there are other feasible options, I try to use them.
LI: I would say I am also conservative with this. In the IMbrave150 trial [NCT03434379] with atezolizumab plus bevacizumab, there were clearly defined exclusions. Our case is somewhat a high-risk patient because they are on an immune modulatory agent like infliximab that tells me, potentially, they were not able to be controlled by steroids. That is a little bit concerning for me. This is an ongoing area of research, particularly for patients with liver transplants on chronic immunosuppressants. Many of us wouldn’t necessarily treat them [with immune modulators] because early retrospective studies have shown high rejection rates. So I think it is very risky, but Dr. Chand I do understand your point about working with gastroenterology to make sure of what is defined as good control versus poor control. It’s a personal decision that is somewhat risky to [proceed with] because there can be significant toxicity when this is introduced in someone that is on immunosuppressants.
VEENA CHARU, MD: What are your thoughts on bevacizumab? In which patients would you not use it? [With] portal hypertension that is systemic? How do you select it?
LI: That is a very good question just because of the potential bleeding risk. In general, I would say I follow what was done in the trials. I do get endoscopy prior to starting treatment and I make sure that varices are treated. If someone has significant varices, particularly gastric varices that cannot be banded or eradicated and which traditionally have been very difficult to treat, I think that would potentially give me pause because those patients are at a very high risk for bleeding. Certainly, [I would not use bevacizumab] in someone who had an acute bleed prior to that. I would say that this in general applies for the tyrosine kinase inhibitors [TKIs] too.
In the National Comprehensive Cancer Network guidelines, atezolizumab plus bevacizumab is the preferred regimen for Child-Pugh A patients.1 Other recommended regimens include sorafenib [Nexavar] and lenvatinib. Sorafenib includes Child-Pugh B7 patients and nivolumab [Opdivo] is useful in certain circumstances based off the CheckMate 459 study [NCT02576509] data for frontline therapy. Even though it wasn’t technically a positive study, it showed some benefit in terms of overall survival but not significant; however, FOLFOX is approved in China.
1. NCCN. Clinical Practice Guidelines in Oncology. Hepatobiliary cancers, version 1.2022. Accessed April 3, 2022. https://bit.ly/3Ao3MZW