Response to Immunotherapy Linked With Improved Liver Function in Advanced HCC

Radiological response to immune checkpoint inhibitors (ICIs) was linked with liver function stabilization or improvement, which correlated with longer survival among patients with advanced hepatocellular carcinoma, in a study published in United European Gastroenterology Journal. Notably, even patients with Child-Pugh class B liver function at baseline experienced improved survival, although large prospective studies are still needed in this subgroup of patients.¹

Hepatocellular carcinoma is known to be driven by various etiologies, including cirrhosis, hepatitis C infection, hepatitis B, alcohol misuse, and metabolic-associated steatohepatitis.² Given these etiologies, a substantial portion of patients diagnosed with hepatocellular carcinoma have impaired liver function due to these underlying conditions. Although patients with Child-Pugh class B liver function at diagnosis have a worse prognosis than patients with Child-Pugh A liver function, they may still see clinically meaningful benefits from treatment for hepatocellular carcinoma.¹

“Importantly, phase 3 clinical trials, which established the current standard-of-care systemic therapies, excluded patients with Child-Pugh class B or C to prevent interference of study results by non-HCC related outcomes,” the study authors explained. “Therefore, no high-level evidence for the treatment of patients with impaired liver function exists. Nevertheless, these patients are commonly receiving systemic therapies in real-world clinical practice.”

Although the amount of real-world evidence demonstrating the safety and efficacy of ICIs in advanced hepatocellular carcinoma has been growing, data on liver function evolution as a prognostic factor for overall survival (OS) are lacking, according to the study authors. Their study assessed liver function evolution among a large real-world cohort of patients with Child-Pugh A or B liver function receiving ICI treatment for hepatocellular carcinoma.

Additionally, they assessed the relationship between radiological response and liver function changes, as well as the proportion of patients whose liver function improved from Child-Pugh B to Child-Pugh A.

Various etiologies, including cirrhosis, hepatitis C infection, hepatitis B, alcohol misuse, and metabolic-associated steatohepatitis, are known to drive liver cancer. | Image credit: Sebastian Kaulitzki - stock.adobe.com

A total of 182 patients treated with ICIs and a control cohort of 160 patients treated with standard-of-care sorafenib were included in the study. The ICI cohort had an average (SD) age of 66.8 (11.8) years. Of the patients treated with ICIs, 74% had cirrhosis, 81% had Child-Pugh class A liver function, and the median (IQR) Child-Pugh score was 5 (5-6).

At 3 months of ICI treatment, 102 patients (52%) showed improved or stabilized liver function, 61 (34%) had worsened liver function, and 19 (10%) were either deceased or missing follow-up data. At 6 months, the results were similar, with 45% of patients experiencing improvement or stabilization of liver function, 30% experiencing deterioration of liver function, and 25% deceased or lost to follow-up. Among those treated with sorafenib, 54 patients (34%) experienced improvement or stabilization at 3 months and 33 (31%) showed improvement or stabilization at 6 months.

Additionally, 16 of 35 patients (46%) who had Child-Pugh B liver function at baseline and received ICIs experienced improvement or stabilization in liver function, and 19 (54%) experienced worsened liver function or were deceased or lost to follow-up at 3 months. Similar trends were seen at 6 months. By 3 and 6 months, 17% and 26% of patients had improved from Child-Pugh B to Child-Pugh A liver function, respectively.

Radiological response to treatment correlated with liver function improvement or stabilization at 6 months, with 73% of responders and 50% of nonresponders showing improvement or stabilization at 6 months. Further, improvement or stabilization at 6 months was liked with better OS (28.4 months; 95% CI, 18.7-38.1 vs 14.2 months; 95% CI, 10.3-18.2; P < .001).

The study was limited by its retrospective nature, as well as reliance on local evaluations of radiological response vs independent centralized review. The sample size is also limited despite being the largest cohort of patients treated with ICIs to be assessed for liver function evolution thus far, the authors noted.

“In conclusion, ICI treatment has the potential to improve or stabilize liver function in patients with well-preserved as well as mild to moderately impaired liver function,” the authors wrote. “Improvement or stabilization of liver function was associated with better OS and was commonly observed in patients with a response to ICI treatment. Large prospective studies in the Child-Pugh B subgroup are warranted to assess safety and efficacy, as well as impact on changes in liver function over time.”

References

1. Pomej K, Balcar L, Sidali S, et al. Evolution of liver function during immune checkpoint inhibitor treatment for hepatocellular carcinoma. United European Gastroenterol J. Published online July 11, 2024. doi:10.1002/ueg2.12626

2. McNulty R. Dr Michael Morse on the etiologies of HCC and treatment options for patients with worsening liver function. The American Journal of Managed Care^®. April 12, 2024. Accessed July 19, 2024. https://www.ajmc.com/view/dr-michael-morse-on-the-etiologies-of-hcc-and-treatment-options-for-patients-with-worsening-liver-function