The presence of NAFLD cirrhosis impacts the best response to immunotherapy in patients with HCC

Disease progression was more likely to be the best response to immunotherapy for patients with hepatocellular carcinoma (HCC) and cirrhosis due to non-alcoholic fatty liver disease (NAFLD).

The presence of cirrhosis due to non-alcoholic fatty liver disease (NAFLD) was associated with significantly higher rates of disease progression as a better response to immunotherapy in patients with hepatocellular carcinoma (HCC) compared to to HCC patients without NAFLD cirrhosis, according to a poster presented at the ASCO Symposium on Gastrointestinal Cancers, held Jan. 20-22, 2022, in San Francisco or online.

Cirrhosis due to NAFLD is one of the main risk factors for developing HCC. Others include cirrhosis due to hepatitis C virus, hepatitis B virus, and alcohol consumption.

“Recent preclinical studies suggest that immunotherapy agents targeted to programmed cell death protein 1 (PD-1) do not cause tumor regression in HCC with underlying NAFLD,” the authors explained.

In a retrospective, single-center study, researchers assessed responses to immunotherapy in patients with HCC who received treatment at UC San Diego Health. Imaging to assess positive responses to treatment was performed between February 2018 and September 2021.

There were a total of 71 patients in the study and they were divided into 2 groups: patients with HCC related to NAFLD cirrhosis (n=14) and patients with HCC without NAFLD cirrhosis (n=57) . The median age was similar between the 2 groups: 66.5 years in the group with NAFLD cirrhosis and 66.0 years in the group without NAFLD cirrhosis.

There was a significantly higher proportion of Latino patients in the group with NAFLD cirrhosis compared to the group without NAFLD cirrhosis (64.3% versus 24.6%; P = 0.01); however, the researchers found that “patients of Latin American descent did not have a significantly higher risk of disease progression compared to non-Hispanic patients.”

The most common immunotherapy regimens in the group with NAFLD cirrhosis were atezolizumab plus bevacizumab (42.9% vs. 36.8%), but the most common immunotherapy regimens in the group without NAFLD cirrhosis was nivolumab (40 .4% versus 28.6%). The remaining regimens were pembrolizumab (14.3% with NAFLD cirrhosis vs 7.0% without), atezolizumab plus cabozantinib (7.1% with NAFLD cirrhosis vs 8.8% without), nivolumab plus PI3K/BRD4 inhibitor (7.1 % with NAFLD cirrhosis vs 3.5% without), and pembrolizumab plus lenvatinib (0% with NAFLD cirrhosis vs 3.5% without).

The disease response results were as follows:

  • Only 11.8% of patients without NAFLD cirrhosis had disease progression as the best response, compared to 35.7% of patients with NAFLD cirrhosis
  • The majority (89.4%) of patients without NAFLD cirrhosis experienced stable disease or partial/complete response versus 64.3% of patients with NAFLD cirrhosis

“There were significantly higher rates of disease progression as a better response to immunotherapy in patients with HCC and NASH cirrhosis compared to those without NASH cirrhosis,” the researchers concluded. “With the widespread use of immunotherapy in patients with HCC, further prospective studies are needed to clarify the impact of the underlying etiology of liver disease on immunotherapeutic response.”

Reference

Chang J, Ryan JS, Ajmera V, Ting S, Tamayo P, Burgoyne A. Responses to immunotherapy in hepatocellular carcinoma patients with nonalcoholic steatohepatitis cirrhosis. Presented at: ASCO Gastrointestinal Cancer Symposium; January 20-22, 2022; San Francisco. Poster 389.

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