Abstract 2555: Real-world data analysis of comprehensive genomic profiling using plasma samples from non-small cell lung cancer patients

Abstract Introduction: Comprehensive genomic profiling (CGP) tests which use plasma samples can detect driver mutations and are recommended when tissue samples are unavailable. Multiple studies have shown that plasma CGP tests can result in genomically matched treatment for cancer patients, especially in gastrointestinal cancer. However, data for non-small cell lung cancer (NSCLC) remain limited. Methods: We searched the database of the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), which comprised 99.7% of the CGP data under insurance coverage in Japan. NSCLC patients analyzed with FoundationOne Liquid CDx (F1LCDx) between August 1 2021 to July 31 2023 were included, all of whom were previously treated. Result: 694 patients with NSCLC underwent liquid biopsy. Among them, 572 cases were adenocarcinoma, and 71 were squamous cell carcinoma. The median age was 68 years (range: 24-93), and 423 patients were male. Pathogenic or likely pathogenic EGFR mutations, ALK rearrangements, ROS1 rearrangements, MET exon 14 skipping mutations, BRAF V600E, RET fusions, ERBB2 mutations, and KRAS G12C were detected in 174 cases (25.1%), 18 cases (2.6%), 2 cases (0.3%), 9 cases (1.3%), 3 cases (0.4%), 7 cases (1.0%), 26 cases (3.7%) and 17 cases (2.4%), respectively. Among the 499 patients without known driver mutations, driver mutations were detected by F1LCDx in 60 patients (12.0%). The detection rate of each driver oncogene is shown in Table 1. Conversely, among the 174, 20, 9 and 3 patients with known EGFR, ALK, ROS1, or BRAF V600E alterations, F1LCDx showed false negative results in 48 (27.6%), 10(50.0%), 8 (88.9%), and 3 cases (100%) (EGFR/BRAF vs. ALK/ROS1, p = 0.001), respectively. Conclusion: In patients without known driver oncogenes, mutations associated with approved therapeutic implications were detected in 12.0%. The detection of gene rearrangements using liquid biopsy may be limited compared with genetic mutations. Genomic profiling detected by FoundationOne Liquid CDx Cases (%) EGFR, known EGFR, unknown ALK, known ALK, unknown ROS1, known ROS1, unknown BRAF V600E, known BRAF V600E, unknown Detected by F1LCDx 126 (72.4) 48 (9.2) 10 (50.0) 8 (1.2) 1 (11.1) 1 (0.15) 0 3 (0.43) Undetected by F1LCDx 48 (27.6) 472 (90.8) 10 (50.0) 666 (98.8) 8 (88.9) 684 (99.9) 3 (100) 688 (99.6) Total 174 520 20 674 9 685 3 691 Citation Format: Momoko Morishita, Koki Fujii, Michiko Ueki, Hiroaki Ikushima, Hideaki Isago, Kousuke Watanabe, Katsutoshi Oda, Hidenori Kage. Real-world data analysis of comprehensive genomic profiling using plasma samples from non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2555.