Abstract 3318: Serum Insulin-Like Growth Factor-1 levels predict outcomes in patients with advanced hepatocellular carcinoma receiving immunotherapy

Abstract Background: The combination of immune checkpoint inhibitors (ICIs) with antiangiogenesis agents or another ICI has become the standard of care for advanced hepatocellular carcinoma (HCC). Elevated serum levels of insulin-like growth factor-1(IGF-1) levels have been previously associated with better outcomes of patients with advanced HCC treated with sorafenib or atezolizumab plus bevacizumab. However, the prognostic value of serum IGF-1 level for other immunotherapy regimens remains unexplored. Methods: Patients with advanced HCC who received anti-PD-1/anti-PD-L1 monoclonal antibody monotherapy or combinations were enrolled. Serum samples were collected prior to initiating immunotherapy, and serum IGF-1 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Based on prior findings from our group, a cutoff value of 63.6 ng/mL was used to stratify patients into high and low serum IGF-1 groups. Patient demographics, tumor characteristics, treatment responses, and survival outcomes were analyzed. Results: From August 2015 to July 2024, 111 patients were enrolled. Baseline characteristics were as follows: 90% male, 71% HBsAg-positive, 18% anti-HCV-positive, Child-Pugh scores: 72% (5 points)/23% (6 points)/5% (7 points), 43% with macrovascular invasion (MVI), 72% with extrahepatic involvement (EHI), and 46% treated with antiangiogenic-containing regimens. Patients with higher serum IGF-1 levels demonstrated fewer adverse clinical features, including lower Child-Pugh scores, ALBI grades, and MVI rates. Patients who achieved an objective response to therapy had significantly higher IGF-1 levels compared to those who did not (57.2 vs. 46.2 ng/mL, p = 0.037). Additionally, patients with high IGF-1 levels exhibited improved overall survival (OS) compared to those with low IGF-1 levels (p = 0.024). When stratified by regimen types, the prognostic value of high IGF-1 levels was maintained in patients treated with antiangiogenic-containing regimens (p = 0.001) but was not observed in patients treated without antiangiogenic agents (p = 0.967). Conclusions: High serum IGF-1 levels are associated with improved OS in patients with advanced HCC, but this prognostic value is confined to regimens containing antiangiogenic agents. These findings underscore the potential of IGF-1 as a biomarker for optimizing immunotherapy strategies in advanced HCC. Citation Format: Tsung-Che Wu, Ching-Tso Chen, Chien-Huai Chuang, Ann-Lii Cheng, Chih-Hung Hsu, Yu-Yun Shao. Serum Insulin-Like Growth Factor-1 levels predict outcomes in patients with advanced hepatocellular carcinoma receiving immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3318.