Updates in Frontline Treatment of Metastatic Liver Cancer - Episode 4

Safety of PD-L1 Inhibitors in mHCC

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Richard S. Finn, MD: Can you talk about toxicity profile? We have 2 intravenous drugs given once every 3 weeks versus sorafenib. There were some very interesting patient-reported outcome and toxicity data presented by Peter Galle at ASCO GI (American Society of Clinical Oncology annual Gastrointestinal Cancers Symposium) earlier in the year.

Richard Kim, MD: First, let’s go over the toxicity profile. In this study, there were no new or unexpected toxicities—effects we see in both arms. It is what we expected. If you look at all grade 3 to 4 toxicity events in both arms, they were about the same. They was slightly more hypertension in the combination arms. As expected, there was more of an issue with hand-foot-skin reaction with the sorafenib arm. It seems like the dose interruption, or any kind of a dose reduction of treatment, was much higher in the arm of sorafenib.

One other thing they looked at is the patient-reported outcome, which is now recognized as the important endpoint of cancer. In this study, they also looked at those data with 2 questionnaires, and they found out a combination of ATEZO (atezolizumab) plus BEV (bevacizumab) delayed the decline in quality of life compared with the study arm of sorafenib. It was comparing 10 months with 4 months.

Not only does the combination really improve the possible overall survival of PFS (progression-free survival) and response rate, but it’s also able to maintain the quality of life with a combination, which is very important when you treat patients.

Richard S. Finn, MD: To have great efficacy data is one thing, but to have this favorable adverse-effect profile and PRO (patient-reported outcome) data is very supportive to making this a frontline go-to regimen. As you highlighted, not everybody will be a candidate for this. One of the issues in liver cancers is that all our phase 3 studies, regardless of stage, have focused on Child-Pugh A patients—patients well compensated with their disease—and that is largely because that’s where we can show an improvement in survival versus patients who are very decompensated and might succumb to their liver failure before cancer-related death.

Things are changing because there are patients who have decompensated liver disease that is maybe driven by the size of their tumor and their tumor burden. This is something we’re going to have to explore moving forward: patients who have large tumor burden, now that we can get responses—and we’ll talk about some of the newer data with upcoming combinations—where we’re seeing consistent responses in the 30% range, plus or minus, that are really benefiting patients and making them feel better. The dataset in Child-Pugh B need to be explored further. Safety is very important in that group.

The other issue that has come up with our patients of underlying liver disease, underlying hepatitis, has been the issue of infection. Amit, as a hepatologist, should we be concerned about treating someone who has hepatitis with these new regimens?

Amit Singal, MD: When we think of hepatitis, there are really 2 types of hepatitis that are most common in the setting of HCC (hepatocellular carcinoma). We think of chronic hepatitis B and chronic hepatitis C. In terms of most of the studies, there is required antiviral therapy and control of hepatitis B. That is standard of care for any agency patient undergoing systemic therapy, particularly because most of these patients have underlying cirrhosis.

In contrast, hepatitis C typically does not need to be treated prior to starting systemic therapy. There are all the data with I/O (immuno-oncology) therapies, as well as TKI (tyrosine kinase inhibitor) therapies, to show that it’s very safe to treat people with active viremia.

Rich, one of the interesting questions that comes up is that as we’ve started to see HCC-related survival improve and survival extend, the question is: Should you consider hepatitis C treatment to reduce the risk of liver-related mortality? We don’t know the answer to that, so it’s not a necessity. You will see potential data come out in terms of evaluating that latter question. Could there be benefit to treating hepatitis C in these patients because of the marked transformation of the systemic therapy landscape?

Richard S. Finn, MD: It’s an important concept because autoimmune hepatitis has been a concern with the PD-1, PD-L1 inhibitors. In reality, that doesn’t seem to be more of an issue in the liver cancer population than others as far as this incident.

Transcript Edited for Clarity