In the last 10 years, clinical outcomes have improved for patients with unresectable hepatocellular carcinoma (uHCC). The cancer generally comes with chronic liver inflammation, and liver cirrhosis is present in up to 80% of cases.
Clinical trials that have tested systemic immunotherapies have excluded patients who don’t fall into the Child-Pugh class A criteria (CP-A) for liver disease, which is the least severe of the Child-Pugh classes A-C. Therefore, there has been much debate about whether patients who have more liver disease (moderate liver dysfunction) and fit under CP-B criteria, instead of CP-A, should be treated with immune checkpoint inhibitor (ICI) therapy or best supportive care (BSC).
A new study, led by Claudia Angela Maria Fulgenzi, MD, with the Department of Surgery and Cancer at the Imperial College London, England, published in JAMA Oncology on July 18, uses an alternative way to compare outcomes following two different paths of care for uHCC patients with moderate liver dysfunction.
How was the study done and what did the investigators find?
Researchers performed a retrospective, multicenter, international clinical case series of patients treated in routine practice in tertiary care centers across Europe, the United States, and Asia. They compared data from uHCC patients with CP-B who were receiving first-line ICI-based treatment regimens (n = 187) with a cohort of matched patients with CP-B receiving BSC (n = 156). The first-line immunotherapies were the monotherapy nivolumab or the combination (atezolizumab plus bevacizumab).
Immunotherapy was linked with significantly lower risk of death, compared with best supportive care.
ICI exposure was associated with a reduction of about 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001).
Is immunotherapy or best supportive care the superior treatment?
The authors wrote that the results point to “improved survival in association with ICI treatment, compared with BSC in patients with uHCC with CP-B liver dysfunction.”
According to the study’s senior author David Pinato, MD, PhD, “this is the first study to suggest that there might be an advantage [of treatment with immunotherapy] in a proportion of people with Child-Pugh B liver dysfunction and particularly so in those patients with more limited disease and portal vein tumor thrombosis.”
Will the findings of this study make treatment allocation for patients with uHCC and moderate liver dysfunction (CP-B) less controversial?
Because it is a retrospective study, Dr. Pinato said in an interview, that the findings are not definitive, but can be used to inform future randomized controlled trials.
Dr. Pinato, who is also with the Imperial College London, added that the findings may also introduce a new question.
Although the study was not powered to look at survival differences across the two immunotherapy options given to the patients, there did not seem to be a striking difference between using one immunotherapy (nivolumab) or a combination (atezolizumab plus bevacizumab), he said.
“This is quite important because we know that combinations are significantly superior to monotherapy in patients with normal liver function but based on our study we might say that this provides preliminary evidence that [superiority of combination therapy] might not be true if the liver function is worse.”