Tocilizumab in fibrolamellar carcinoma.

Abstract

e16252 Background: Fibrolamellar Carcinoma (FLC) is a rare liver cancer of young people. Interleukin-6 (IL-6), is overexpressed in many cancers, including FLC, drives inflammation, angiogenesis, and activation of the JAK-STAT signaling pathway associated with progression, a worse prognosis, and inhibition of T-cell tumor attack. Check-point inhibitor (CPI) drugs induce T-cell tumor attack, but also induce immune-related adverse effects (irAEs), often with elevated IL-6 and eosinophilia. Tocilizumab (TOC), an IL-6 receptor blocker, approved for inflammatory diseases and steroid-refractory CPI irAEs, has been shown in the lab to both mitigate CPI toxicity and promote tumor immunity, while avoiding the toxicity, immune suppression, and tumor promoting effects of steroids, and allowing patients to restart CPIs. We prospectively collected data over 18 months on all FLC TOC patients seen and report on those with irAEs. This is the first report of TOC use in FLC. Methods: With IRB approval and consent (NCT03793088), data was collected prospectively on all FLC TOC subjects from Apr. 1, 2023 to Jan. 28, 2025. Results: Overall, 83% of 24 FLC patients with irAEs responded to TOC (13F, 14M, median age 24, 50% recent CPI, 92% AE grade 3-4, 1/3 with concurrent steroids). The most common irAEs were ascites, hepatitis, pneumonitis and colitis, with a median serum IL-6 of 163 [< 5 pg/ml], median tumor IL-6 overexpression at the 96 Th percentile, and median 9% eosinophilia [ < 2%]. The median tumor volume and circulating tumor DNA response was -20% and -78%, respectively. Proximal follow-up scans showed CR/PR/SD/PD rates of 5%/40%/40%/15%. Most (74%) resumed CPI after TOC treatment and 41% continued TOC as maintenance. Best tumor responses corresponded with CR for irAE, higher IL-6, CPI continuation, and no steroids. No side effects were attributed to TOC (total 174 doses). Conclusions: TOC used for IL-6 mediated inflammatory conditions in FLC showed reliable responses, with many patients restarting CPI, and a majority with tumor burden reduction, suggesting a double benefit. These early data are considered hypothesis generating and can help justify development of randomised clinical studies.