Abstract 5086: Effects of immune negative genes on immunotherapy combined anti-vascular for liver cancer

Abstract

Abstract Background: In recent years, the application of immune checkpoint inhibitors (ICIs) therapies targeting the programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) or cytotoxic T lymphocyte (CTLA-4) pathway represents a major breakthrough in many types of cancer. However, low response rates has limited the clinical application of ICIs monotherapy for liver cancer.Anti-vascular combined ICIs are the preferred regiments in first-line systemic treatment of hepatocellular carcinoma (HCC) by NCCN. Therefore, strategies to improve efficacy through patient stratification, biomarker-directed therapies or combinations remain urgently needed. The purpose of this study was to explore potential genomic markers associated with “low response rates” in liver cancer with ICIs combination therapy. Methods: Between July 2019 and April 2021, a total of 47 patients with advanced liver cancer treated with ICIs combined anti-vascular or anti-vascular alone therapy were admitted to Drum Tower Hospital. We retrospectively identified genomic markers, abstracted clinicopathologic features and treatment outcomes. Results: 47 patients with advanced liver cancer treated with immunotherapy combined anti-vascular or anti-vascular were included in this analysis. 40 of 47patients (85.1%) were male and the median age was 58 years (range, 32 to 80 years). Most patients (85.1%) were HCC and 12 patients had at least one immune negative gene mutation (including CCND1, FGF19, FGF3, FGF4, KEAP1, JAK1, MDM4, DNMT3A, EGFR and STK11). Median follow-up was 206 days in immunotherapy combined anti-vascular group and 215 days in anti-vascular group. In the immunotherapy combined anti-vascular group, compared with wild-type, patients with immune negative gene mutations were significantly associated with poorer overall survival (P=0.021). In anti-vascular alone group, there was no significant difference in median OS for patients with/without immune negative gene (P=0.94). In addition, patients with immune negative gene mutations, OS of anti-vascular alone was better than immunotherapy combined anti-vascular (P=0.085). Conclusion: Our study revealed that liver cancer with immune negative gene mutations have a worse prognosis than wild-type patients on immunotherapy combined anti-vascular. In addition, in patients with immune negative gene mutations, immunotherapy combined anti-vascular did not significantly improve prognosis compared to anti-vascular alone. Citation Format: Xinhua Zhu, Yanan Chen, Junling Zhang, Mengli Huang, Xihua Xia. Effects of immune negative genes on immunotherapy combined anti-vascular for liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5086.