Clinical Outcomes in Fibrolamellar Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors

Simple Summary Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer that affects children and young adults. Although immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-CTLA-4 are becoming standard of care in various cancers, including other forms of liver cancer, few studies have examined the safety and efficacy of ICIs in FLC. This study represents the largest multicenter, retrospective cohort of FLC patients receiving ICIs alone and in combination with other drugs. Our results demonstrate that ICIs have modest clinical benefit in the treatment of FLC. Results of this analysis have important implications for the management of patients with FLC and will inform future treatment decisions. Background: Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer primarily affecting children and young adults. Although considered a subset of hepatocellular carcinoma (HCC), FLC has unique molecular and pathologic characteristics, suggesting that it may require different treatment. Immune checkpoint inhibitors (ICIs) are used in the treatment of HCC, but efficacy and safety in FLC has not been characterized. Methods: We performed a multicenter retrospective analysis of patients with FLC to determine responses to ICI therapy. Response rates were assessed based on RECIST 1.1 criteria, and Kaplan-Meier statistics were used for progression-free survival (PFS) and overall survival (OS). Results: FLC tumors were characterized by low tumor mutational burden (TMB) and absent PD-L1 expression. We identified 19 patients who received ICIs, including 15 who received ICI therapy alone [programmed death receptor 1 (PD-1) inhibitor, +/- cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitor]. Objective tumor responses were observed in 3/19 patients (15.8%), including 2/15 patients (13.3%) who received ICIs alone, all partial responses. Median PFS and OS were 5.5 and 26.0 months, respectively. Grade 3-4 immune related adverse events were observed in 4/19 (21.1%) patients. Conclusions: ICI therapy has modest clinical activity in FLC, and novel therapeutic combinations are needed.