Dina Ioffe, MD: The Importance of Liver Function in Unresectable HCC

Dina Ioffe, MD, discusses the importance of liver function in the treatment of unresectable hepatocellular carcinoma. She also explores data from the HIMALAYA trial on 5-year overall survival outcomes by liver function with durvalumab plus tremelimumab treatment.

Transcript

SPEAKER_00 0:08

My name is Dina Yafee. I'm an assistant professor at Fox Chase Cancer Center in Philadelphia. I specialize in gastrointestinal cancers, specifically liver cancer. Liver function matters tremendously when treating unresectable hepatocellular carcinoma and really guides most of our decision making, specifically when talking about systemic therapy options. So patients who have lower baseline liver function have inferior treatment and survival outcomes. And it's very common for a lot of patients who have unresectable batocellular carcinoma or HCC to die from their cirrhosis or underlying liver dysfunction that contributed or led to the development of liver cancer rather than dying directly from progression of their cancer. There are two methods or two grading systems that we use to measure liver function. Most commonly is the child Pew classification, which uses some lab values as well as subjective measures of portal hypertension, including ascites and hepatic encephalopathy. This is primarily validated in patients who have cirrhosis. And then there's also the Albi grading score, albumin-bilirubin score, which is validated in patients with HCC and is more specific to patients with HCC who don't necessarily have cirrhosis. Within the child Pew classification, child Pew A indicates mild or no hepatic dysfunction, child Pew B indicates moderate dysfunction, and child Pew C indicates severe liver dysfunction. Similarly, within the Albi grading system, increasing score indicates increasing levels of liver dysfunction or decompensation, with an Albi grade 1 score indicating mild liver dysfunction, grade 2 indicating moderate liver dysfunction, and grade 3 indicating severe liver dysfunction. Typically, most clinical trials include patients with child PU class A liver dysfunction, meaning minimal liver dysfunction, though it can still include patients with some degree of decompensation, even including ascites, prior hepatic encephalopathy, or prior variceal bleeding. The incorporation of albae scores refines mortality risk better across all stages of liver cancer. But in most, as of now, most clinical trials use child Pew classification as part of their inclusion criteria. The Himalayas trial evaluated the use of dervalimab and tremolimimab in patients with advanced unresectable HCC and demonstrated a survival benefit over an investigator's choice of TKI, seraphonib, or lymbatinib. There's post hoc analysis that looks at patients with a baseline Albi score of grade two or three, and it shows that there is a the survival benefit persists in this group as well. So in the stride group, which is the dervalimab plus tremolimimab group, the median overall survival was 11.3 months in patients with a baseline Albi grade two or three versus in the seraphonib group 9.7 months. Importantly, at one and a half years or 18 months, 36% of patients in the stride group were still alive compared to 29% in the seraphnob group. And at five years, 13.7% were alive in the stride arm versus 4.7% in the seraphonib group. These are not usually reported in other clinical trials, and a lot of our patients present with more advanced liver dysfunction than we may typically see in clinical trials. So it's hard to know how to generalize some of these studies to our patients who may have had more liver-directed therapies that sometimes can lead to some degree of liver dysfunction. And by the time they get to see a medical oncologist, they may not have an Albi grade one or child PUA. So having this data from the Himalaya study is really important that, and it demonstrates that these patients still benefit from systemic therapy even with some degree of liver dysfunction. Interestingly, there was also data from the Himalaya study that showed there wasn't a significant decrease in algae scores over time in the stride arm of the Himalaya study, although this was a post hoc analysis that was not powered for statistical significance. Whereas in the seraphonib arm, there was some progressive decline in liver function.