Real-World Evidence on the Efficacy of Icaritin for Unresectable Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Study

Icaritin's efficacy was evaluated for unresectable advanced hepatocellular carcinoma (HCC), a major global burden with limited advanced-stage treatment options. A multicenter retrospective real-world study (May 2022–May 2024) included 163 patients with unresectable advanced HCC. Treatments were Icaritin monotherapy, Icaritin + anti-VEGF, or Icaritin + PD-1 inhibitors + anti-VEGF. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Subgroup analyses assessed alpha-fetoprotein (AFP) impact. In first-line treatment, Icaritin monotherapy achieved an ORR of 26.32%. Combining Icaritin with PD-1 inhibitors and anti-VEGF agents increased ORR to 38.30%. Median PFS was 4.27 months for monotherapy; second-line median OS for Icaritin monotherapy reached 19.91 months. Patients with AFP < 400 ng/mL generally showed numerically better PFS in first-line regimens compared to those with AFP ≥ 400 ng/mL. Patients with high AFP treated with Icaritin + PD-1 inhibitors demonstrated a promising response. Icaritin shows promising efficacy in unresectable HCC, particularly in patients with lower AFP levels. The findings support personalized treatment strategies and warrant further research to optimize outcomes and elucidate Icaritin's mechanisms.