Abstract 426: Targeted genome profiling in patients with advanced hepatocellular carcinoma treated with sorafenib

Background/Objectives: Sorafenib is the only approved targeted agent as first-line treatment for advanced hepatocellular carcinoma (HCC). Unfortunately, many HCC patients are initially not responsive to sorafenib. Due to anatomic limitations and underlying liver dysfunction, genomic studies of HCC patients have not been actively pursued yet compared to other solid tumors; especially, in sorafenib-treated subset. In this study, we have retrospectively identified advanced HCC patients who had archival tumor tissues available for targeted genomic sequencing and who had been treated with sorafenib. Methods: We performed targeted genomic profiling for 381 cancer-related genes from 42 HCC (32 hepatitis B virus-related, 1 alcohol-related, 7 unknown) patients treated with sorafenib at Samsung Medical Center, Seoul, Korea from July 2008 to October 2013. We excluded 2 patients who were lost to follow up for evaluation of treatment response to sorafenib. Results: Of the 40 patients, there were 5 confirmed PRs, 7 SDs, and 28 PDs. In 40 patients, there were 6 CDKN2B amplifications, 4 NTRK1 amplifications, 2 MET amplifications, 2 FGF19 amplifications, 2 CCND1 amplifications, 1 EGFR amplification, 1 FGF23 amplification and 1 CCNE1 amplification. In cell cycle-related genes, those patients with aberrations were less likely to respond to sorafenib. Of note, two patients whose tumor had CCND1 amplifications had de novo resistance to sorafenib. Conclusions: Our study demonstrates inter-patient heterogeneity in advanced HCC patients and the role of cell cycle-associated genes in resistance mechanism to sorafenib is being investigated. Citation Format: Wonseok Kang, Kyung Kim, Joon Hyeok Lee, Ho Yeong Lim, Woong-Yang Park, Jeeyun Lee, Yong Han Paik. Targeted genome profiling in patients with advanced hepatocellular carcinoma treated with sorafenib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 426. doi:10.1158/1538-7445.AM2017-426