The activity and safety of icaritin for patients with unresectable HCC: A real world, retrospective study.

e16181 Background: Primary liver cancer is a major health burden globally, ranking sixth in incidence and third in mortality among all cancers1. Over the past 5 years, immune checkpoint inhibitors (ICIs) and multi-targeted tyrosine-kinase inhibitors have emerged as new treatment options for advanced hepatocellular carcinoma2–4. Nevertheless, only a small subset of patients with hepatocellular carcinoma derive a response to ICI monotherapy. Icaritin, a target tumor micro-environment(TME) modulating compound, which interacts with MyD88/IkB kinase-a (IKK)5, inhibiting the TNF-a-induced IKK and nuclear factor-κB (NF-kB) signaling pathways and blocking PD-L1 expression in HBV-related HCC6-9 and has been approved in China for the treatment of first-line advanced HCC. Icaritin phase III study previously reported at 2021 ASCO, we therefore investigated the efficacy of icaritin in patients with unresectable stage IIA-IIIB (CNLC stage) HCC in a real-world setting. Methods: This multi-center, retrospective study, conducted between May 2022 and Nov 2023. We retrospectively collected medical records of patients (pts) with unresectable IIA-IIIB (CNLC stage) HCC who received icaritin monotherapy (mono-group) or icaritin combined with PD-1/L1 and/or anti-VEGF therapy (combination group) as first line therapy. The primary endpoints were progression free survival (PFS); Secondary endpoints included overall survival (OS) rate, objective response rate (ORR) by RECIST v1.1, and safety. Results: Patients characteristics: 49 pts were eligible for inclusion with median age of 60.7 years old (range 18.0-89.0), 91.8% were ECOG PS 0-1, 86.5% had HBV infection, 79.6% were stage III and 48.9% were AFP>400 ng/ml. 33 pts administrated with combination therapy, other 16 pts’ regimen was icaritin monotherapy. Efficacy: As of the data cutoff for the preliminary analysis of progression free survival (Nov 30, 2023), the median follow-up was 11.17 months (95%CI 6.74–12.12). The ORR for the combination group was 6.06%, and 12.50% for the mono-group, the mPFS was 8.94(95%CI 6.90~9.76) and 5.52 (2.92~NE) for each group. The mOS was not reached for both group, the 6 and 12-months OS rates were 91.00% and 73.67% respectively. Safety: For the safety information, most of TRAEs were grade 1 or 2. No serious AEs were observed. Conclusions: This real-world retrospective study revealed that icaritin monotherapy and icaritin-based combination therapy are promising therapeutic options for unresectable HCC in China. Clinical trial information: ChiCTR2300074565.