Abstract 3547: The BIM deletion polymorphism not associated with treatment efficacy of sorafenib for advanced hepatocellular carcinoma.

Abstract

Abstract Background: A germline BIM deletion polymorphism was recently proposed to predict poor treatment efficacy of certain kinase inhibitors, including imatinib and gefitinib. Sorafenib, a multi-kinase inhibitor, is the current standard treatment for advanced hepatocellular carcinoma (HCC). We aimed to explore whether BIM deletion predicted the treatment efficacy of sorafenib for advanced HCC. Methods: All patients who were enrolled in clinical trials to receive sorafenib-containing regimens as first-line therapy for advanced HCC and consented to provide peripheral blood samples were included in the study. Genomic DNA was extracted from the mononuclear cells of peripheral blood. We performed PCR and agarose gel electrophoresis to detect the genotypes with and without the BIM deletion polymorphism, and then analyzed the associations between BIM genotypes and treatment outcomes. Results: A total of 90 patients were enrolled. Among them, 64 patients received sorafenib plus metronomic tegafur/uracil, and 26 patients received sorafenib alone; 69 (77%) patients had chronic hepatitis B infection, and 18 (20%) had chronic hepatitis C infection. Most (90%) patients had BCLC stage C disease. The heterozygous BIM deletion polymorphism was identified in 9 (10%) patients. Patients with and without the BIM deletion polymorphism had similar objective response rates (12.5 % vs. 6.2%, p = 0.479) and disease control rates (55.6% vs. 60.5%, p = 0.774). Time to progression, progression-free survival, and overall survival were also similar between patients with and without BIM deletion (Table), regardless the treatment regimens. Besides, the BIM polymorphism had no associations with gender, age, hepatitis etiology, and disease stage. Conclusions: The BIM deletion polymorphism was not associated with the treatment efficacy of sorafenib for advanced HCC. (This work was supported by grants NSC98-3112-B-002-038, NSC101-2314-B-002-141, 100CAP1020-2 & NTUH.101-N1965.) BIM deletion & treatment outcomes BIM deletion polymorphism Yes (n = 10) No (n = 80) p value Time to progression 4.2 (0–10.5) 4.1 (3.6–4.7) 0.978 Progression-free survival 4.2 (0–10.5) 3.7 (2.7–4.8) 0.871 Overall survival 8.1 (0–187.1) 7.4 (5.6–9.1) 0.742 Data presented as median (95% confidence interval), in months Citation Format: Yu-Yun Shao, Yung-Lin Chang, Chung-Yi Huang, Chih-Hung Hsu, Ann-Lii Cheng. The BIM deletion polymorphism not associated with treatment efficacy of sorafenib for advanced hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3547. doi:10.1158/1538-7445.AM2013-3547