Abstract 5582: Liquid biopsy-based comprehensive genomic profiling reveal mutational landscape in real-world patients with unresectable NSCLC

Abstract

Abstract Introduction: NSCLC accounts for more than 80% of all lung cancer, and has been shown for clinical benefits from targeted therapies, according to tests of multiple genes, such as EGFR, KRAS, ALK, ERBB2. Previous studies revealed molecular characteristics and responses of targeted therapies in NSCLC. However, most studies used tissue biopsies. There is increasing interest to characterize the molecular profile of NSCLC through liquid biopsy. Hence, here we report a comprehensive genomic profiling study in unresectable NSCLC patients using liquid biopsy. Methods: The prospective study is part of the Predicine’s Phoenix Program, a global molecular biomarkers screening program in multiple solid tumors. Currently, the study enrolled 352 unresectable advanced NSCLC patients from 24 centers in China, who were naïve to the 1st line treatment or recurrent after 1st line targeted therapies. 10ml of blood was collected from each patient and delivered to a central lab for ctDNA analysis. The study applied PredicineCARE, an NGS-based liquid biopsy assay, to profile somatic mutations, copy number variations, and gene fusions among these patients. Results: The study identified 1614 somatic mutations and 202 copy number variants among blood samples from 352 patients. The most common altered genes were TP53(176/352, 50%), EGFR(144/352, 41%), PIK3CA(35/352, 10%), CDNK2A(35/352, 10%), KRAS(28/352, 8%), and RB1(28/352, 8%). Gene copy number gain incidents were identified on MYC(n=22), PIK3CA(n=16), EGFR(n=15), and MET(n=7), etc. Notably, the study also reported gene copy number loss incidents through liquid biopsy, such as CDKN2A(n=16), PTEN(n=11), and RB1(n=10). The study identified 12 gene fusion incidents, including 7 EML4-ALK fusions, 2 RET fusions(KIF5B-RET and NCOA4-RET), 2 NTRK fusions(ETV6-NTRK3 and NOS1AP-NTRK1), and 1 rare CD74-NRG1 fusion. Conclusions: This study revealed the comprehensive mutational landscape of advanced NSCLC through liquid biopsy, providing novel biomarkers for clinical diagnosis and targeted therapy mechanism studies. Citation Format: Haoran Tang, Feng Xie, Yue Zhang, Shidong Jia. Liquid biopsy-based comprehensive genomic profiling reveal mutational landscape in real-world patients with unresectable NSCLC. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5582.