Abstract Background Patients with liver cirrhosis or HCC were found to have decreased serum IGF-1 levels. Serum IGF-1 levels have been shown to predict the prognosis of patients with various types of cancer. Whether the IGF-1 levels can predict the treatment efficacy of anti-angiogenic therapy for advanced HCC remained unknown. Methods Advanced HCC patients, enrolled in a phase II study (Hsu et al: J Hepatol 2010) and its extended cohort, were treated with sorafenib plus metronomic oral tegafur/uracil until disease progression. Serum samples were collected before treatment and 4 weeks after the start of treatment. The levels of IGF-1 and IGF-2 were determined by ELISA. The baseline levels and post-treatment changes of these factors were analyzed for their associations with treatment outcomes. Results Among 68 pts treated with the protocol treatment, 64 were enrolled to this study. Among them, 57 (89%) were male, 49 (72%) were chronically infected with hepatitis B virus, and 40 (63%) had extrahepatic metastasis. All patients had liver reserve graded as Child-Pugh class A. There were 4 partial responder (PR) and 33 patients with stable disease (SD) according to RECIST 1.0. The disease control rate (DCR, defined as PR+SD) was 58%. The median PFS and OS were 3.7 and 7.4 months, respectively. Both IGF-1 and IGF-2 levels significantly decreased after treatment (p < 0.001 and p < 0.001, respectively), but the post-treatment changes were not associated with treatment response or disease control. Patients with higher (≥ median) baseline IGF-1 levels, compared to those with lower levels, had significantly better disease control rates (DCR, 72% vs. 44%, p = 0.023) and longer PFS (median, 5.6 vs. 2.0 months, p = 0.034). OS was also longer in patients with higher baseline IGF-1 levels, but with borderline significance only (median, 8.1 vs. 5.0 months, p = 0.052). In multivariate analysis including all clinicopathologic variables with potential predictive values, high baseline IGF levels remained as an independent predictor for longer PFS (p = 0.008). Baseline IGF-2 levels were not found to be associated with treatment outcomes. Conclusions High baseline IGF-1 levels can predict better treatment efficacy of anti-angiogenic therapy for patients with advanced HCC. (This study was supported by the grant of NSC 98-3112-B-002-038.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4128. doi:10.1158/1538-7445.AM2011-4128