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ASCO GI 2026 | Immunotherapy in hepatocellular carcinoma with impaired liver function
Stephen Lam Chan, MD, FRCP, Chinese University of Hong Kong, Hong Kong, China, describes the expansion of immunotherapy to patients with hepatocellular carcinoma (HCC) and poor liver function, highlighting the need to balance efficacy and toxicity. While immunotherapy regimens are generally well-tolerated, patients with severe liver dysfunction may not benefit and may experience increased adverse events. The choice of regimen should be guided by prospective trial data, such as the SIERRA study (NCT05883644) of tremelimumab and durvalumab. This interview took place at the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium in San Francisco, CA.
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Transcript
So traditionally, most of the clinical trials for HCC, they only recruit patients with Child-Pugh A and exclude patients with Child-Pugh B or any evidence of liver failure. And this is understandable because traditionally the TKI or even chemo, they have the problem of leading to hepatotoxicity. But nowadays, we know that the immunotherapy regimen, generally, they are well-tolerated and less hepatotoxic...
So traditionally, most of the clinical trials for HCC, they only recruit patients with Child-Pugh A and exclude patients with Child-Pugh B or any evidence of liver failure. And this is understandable because traditionally the TKI or even chemo, they have the problem of leading to hepatotoxicity. But nowadays, we know that the immunotherapy regimen, generally, they are well-tolerated and less hepatotoxic. So it makes sense to expand the population that may be benefited from this immunotherapy regimen. But when we test the immunotherapy in this population, there’s still some consideration. First, we know that the worse the hepatic function, still the survival is not good. It’s a poor prognostic feature. And also, we need to select the right patients. If the patients really have bad liver-like Child-Pugh C or evidence of decompensation, they still do not benefit from the immunotherapy. Another point we need to look at is the mechanism of the drugs. For example, for PD-1 alone, of course, it is least toxic, but maybe the response rate is not high or the survival benefit is not high. But we move ahead to use the VEGF combination. Sometimes the bleeding and the events may be higher. While when you use the immunocombination like CTLA-4, PD-1, they don’t have any VEGF problems, but the problem is there may be higher immune-related AE. So I think finally it’s a balance of these factors for us to decide which regimen to use. But finally, we need to be guided by the prospective trial data. So in the ASCO GI this year, I will present some of the data about the real world and also the clinical trials, especially the Sierra study about the tremelimumab and durvalumab. And what we learned that is relatively safe in the populations. But of course, we need to wait for longer survival follow-up to reflect the efficacy data to be used. And finally, another point I would like to mention for these populations, they are still prone to develop liver failure. So we need to choose a regimen that could preserve the hepatic function or avoid the too early deterioration of liver function is also important.
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