Abstract 181: Pan-cancer clinical genomic profiling in circulating tumor DNA from 7345 Chinese advanced cancer patients

Abstract

Abstract Purpose: Circulating tumor DNA (ctDNA) sequencing was implemented widely in advanced cancer patients for guiding matched therapy, which could avoid invasive specimen collection and tumor heterogeneous. However, clinical ctDNA genomic profiling of Chinese advanced pan-cancer patients is still unknown. Methods: 7624 blood samples were obtained from 7345 Chinese patients with advanced solid tumor, including 3506 lung cancer, 860 liver cancer, 674 colorectum cancer, 343 stomach cancer, 329 biliary tract cancer, 324 breast cancer, and 1588 other 17 tumor types. Genomic alterations (GAs), including SNV/Indels, CNVs, and rearrangements were identified via ctDNA sequencing with a 150 cancer-related gene panel. Potentially actionable GAs was annotated according to OncoKB database. Results: There are 85.2% (6497/7624) samples harbors maximum somatic allele frequency (MSAF) >0.3% and average 5.5 GAs per samples. 21253 known or likely deleterious alterations were identified in 137 genes, and average 3.3 known or likely deleterious GAs per samples. Additionally, 38.4% (2930/7624) samples had at least one potentially actionable GA (PAGA). The most frequently and potentially actionable altered genes were EGFR (13.2%), KRAS (8.6%), PIK3CA (5.1%), ERBB2 (4.0%), FGFR1 (3.6%) and BRAF (3.3%). Importantly, PAGAs in RTK-RAS-MAPK pathway was the most common with 33.7% samples (19.2% SNV/Indels only, 9.8% CNVs only, 1.4% rearrangements only, 3.4% either two or more types of alterations), followed by 5.9% PI3K/AKT/mTOR pathway, 2.1% TP53/cell cycle pathway, 0.8% Epigenetic pathway, 0.1% Hedgehog pathway, and 0.1% DDR pathway. The samples of at least one PAGA in aforementioned pathways were 53.1% in breast cancer, 49.6% in colorectum cancer, 44.0% in bladder/urinary tract cancer, 43.5% in lung cancer, 39.4% in stomach cancer, respectively. In all, 287 cases with PAGAs in RTK-RAS-MAPK pathway (ROS1, ALK, MET) could benefit from crizotinib; 49 cases with PAGAs in RTK-RAS-MAPK pathway (BRAF) could benefit from vemurafenib; 447 cases with PAGAs in PI3K/AKT/mTOR pathway (PIK3CA, PTEN, AKT1, mTOR) could benefit from everolimus; and 6 cases with PAGAs in DDR pathway (ATM) could benefit from olaparib. Conclusions: The study revealed a comprehensive ctDNA genomic profiling of Chinese patients with advanced solid tumors. And further larger cohorts validation for ctDNA sequencing as a diagnostic tool in target-therapy is needed. Citation Format: Wenhua Li, Hui Chen, Yifan Zhou, Danpeng Sun, Bei Zhang, Yuezong Bai, Qingqing Ding. Pan-cancer clinical genomic profiling in circulating tumor DNA from 7345 Chinese advanced cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 181.