Abstract 4333: High incidence of ERBB2 amplification associated with microsatellite stable status in Chinese colorectal cancer patients

Abstract

Abstract Introduction: Amplification of receptor tyrosine-protein kinase erbB-2 gene (ERBB2), also known as HER2, can serve as an effective biomarker for either dual targeted therapy with trastuzumab plus lapatinib or pertuzumab plus trastuzumab in treating refractory metastatic colorectal cancer (CRC) as shown in HERACLES and MyPathway clinical trials. Next-generation sequencing (NGS) based comprehensive genomic profiling (CGP) has increasingly proven to be a valuable analysis and detection method that can make a significant impact on cancer treatment decisions. Experimental Procedure: Comprehensive genomic profiling was performed with a 450-gene next-generation sequencing (NGS) panel on both FFPE tumor and matched blood samples from a cohort of 123 Chinese colorectal cancer patients comprising 76 males and 47 females (median age was 60). All classes of genomic alterations including single-nucleotide variations, short and long insertions and deletions, copy number variations, and gene fusions were detected. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were also determined by algorithms-based NGS data. Results: The most common altered genes in the 123 CRC Chinese patients were TP53 (71%), APC (70%) and KRAS (50%). 19 pts were detected by NGS as MSI-high with a median TMB value of 119 muts/Mb, which was significantly higher than in the MSS subgroup (104 pts) with a median TMB value of 10 muts/Mb (p-value was 1.5E-08). In total, 9% of the CRC pts harbored ERBB2 amplifications (11/123) by NGS panel, and it was much higher than 3-4% in Western populations. Interestingly, all 11 ERBB2 amplified cases were presented exclusively in the MSS subgroup (11/104, 11%), and were all BRAF wild-type. Five out of the 11 cases were KRAS wild-type. In addition, 9 confirmed somatic ERBB2 point mutations in the COSMIC database were detected in 7 CRC pts (7/123, 6%), including T166M, S280F, A324T, R678Q, V812I, L725S, V842I and H848Y. Four pts were MSI-high. Conclusion: CGP reveals significantly higher prevalence of both amplifications and point mutations of ERBB2/HER2 in Chinese CRC patients, compared with Western population. It may identify a subgroup of CRC patients potentially benefiting from specific targeted therapies including anti-HER2 therapies. Moreover, the highly exclusive presence of ERBB2 amplifications with MSS status could provide these patients with broader precision treatment opportunity. Citation Format: Sen Zhang, Yun Guo, Jun Jia, Weibin Shu, Hui Li, Yu Wang, Wei Zhao, Zusen Wang, Xueqing Yao, Tao Xiang, Yong Li, Ting Deng, Weifeng Wang, Kai Wang. High incidence of ERBB2 amplification associated with microsatellite stable status in Chinese colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4333.