Presence of NAFLD Cirrhosis Impacts 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 nonalcoholic fatty liver disease (NAFLD).

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

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

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

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

There was a total of 71 patients in the study and they were split 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 were a significantly higher proportion of Latino patients in the group with NAFLD cirrhosis compared with the group without NAFLD cirrhosis (64.3% vs 24.6%; P = .01); however, the researchers found that “patients of Latino ethnicity were not found to have a significantly higher risk of disease progression compared to non-Latino patients.”

The most common immunotherapy regimens in the group with NAFLD cirrhosis was atezolizumab plus bevacizumab (42.9% vs 36.8%), but the most common immunotherapy in the group without NAFLD cirrhosis was nivolumab (40.4% vs 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 findings on disease response were:

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

“There were significantly higher rates of disease progression as the best response to immunotherapy in patients with HCC and NASH cirrhosis compared to those without NASH cirrhosis,” the researchers concluded. “With the expanded use of immunotherapy in HCC patients, further prospective studies are needed to clarify the impact of underlying liver disease etiology on immunotherapy 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 Cancers Symposium; January 20-22, 2022; San Francisco. Poster 389.