1557P - A large scale prospective concordance study of oncogene driver detection between plasma- and tissue-based NGS analysis in advanced non-small cell lung cancer (NSCLC)

Liquid biopsy-based next-generation sequencing (NGS) is clinically useful as a less invasive multi-gene analysis for precision cancer medicine. However, performance of NGS using plasma cell-free DNA (cfDNA) compared to tumor tissue has not been evaluated in a large-scale sample. A liquid biopsy study is additionally conducted in the nation-wide lung cancer genome screening project (LC-SCRUM-Japan), targeting 2000 NSCLC patients. Tumor genetic alterations are evaluated by cfDNA- and tissue-based NGS tests. Plasma is collected within 4 weeks of the corresponding tissue biopsy. cfDNA is analyzed using Guardant360Ⓡ (investigational device exemption version, Guardant Health); tumor tissue is analyzed by Oncomine Comprehensive AssayⓇ version 3 (Thermo Fisher Scientific). We assessed the detectability of 8 oncogene drivers: mutations of EGFR, KRAS, BRAF, ERBB2 and MET, and fusions of ALK, RET and ROS1. As of March 2019, 270 advanced NSCLC patients were enrolled. Median age was 67 (range, 30-87) years, 169 patients (63%) were men, 86 (32%) were nonsmokers, 215 (80%) had adenocarcinoma, 206 (76%) were stage IV, and 224 (83%) received no prior chemotherapy. An oncogene driver was detected in 156 patients (58%) by at least one NGS method, including 138 (51%) in tissue and 107 (40%) in cfDNA. Using the tissue assay as a control, the positive percent agreement (PPA) of gene mutations in the cfDNA assay was 75% (91 of 121), including 74% (53 of 72) for EGFR, 78% (31 of 40) for KRAS, 100% (3 of 3) for BRAF, 75% (3 of 4) for ERBB2 and 50% (1 of 2) for MET. The PPA of gene fusions in the cfDNA assay was 24% (4 of 17), including 33% (2 of 6) for ALK, 33% (2 of 6) for RET and 0% (0 of 5) for ROS1. Of 132 patients in whom no oncogene driver was detected by the tissue assay, 17 had the drivers detected in cfDNA: 8 EGFR, 5 KRAS, 1 BRAF, 1 ERBB2, 1 MET and 1 ALK. In the cfDNA-based NGS, the detectability of gene mutations was comparable with the previously reported single-gene tests using cfDNA, whereas that of gene fusions was low. The cfDNA-based assay may be useful for patients in whom oncogene driver detection was failed by the tissue-based assay. This study is now ongoing and we will present updated results. UMIN000030496. National Cancer Center. Guardant Health, Merck Serono. S. Matsumoto: Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Resear