Clinical utility of comprehensive genomic profiling in non-small cell lung cancer: An analysis of a nation-wide database

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2025-02, Vol.200, p.108099, Article 108099
• Main Authors: Fujii, Koki, Ueki, Michiko, Morishita, Momoko, Ikushima, Hiroaki, Isago, Hideaki, Watanabe, Kousuke, Oda, Katsutoshi, Kage, Hidenori
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Companion diagnostics; Comprehensive genomic profiling; Databases, Factual; Databases, Genetic; Female; Genomic testing; Genomics - methods; Germline variants; Humans; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Male; Middle Aged; Mutation; Non-small cell lung cancer; Prognosis
• ISSN: 0169-5002; 1872-8332; 1872-8332
• DOI: 10.1016/j.lungcan.2025.108099

•25% of patients previously negative for driver mutations were positive with tissue CGP.•Detection rates for gene fusions are lower than gene mutations with tissue CGP.•Detection rates of mutations and fusions are lower with plasma CGP than tissue.•Presumed germline pathogenic variants were detected in 3.9–5.4% of NSCLC patients. Molecular testing is recommended to patients with advanced non-small cell lung cancer (NSCLC) because those who receive targeted therapy have better prognosis than patients who don’t. However, recent studies have raised concerns that first-line companion diagnostic testing at diagnosis may have lower detection rates than previously reported. Therefore, we sought to determine the utility of comprehensive genomic profiling (CGP) tests in NSCLC by analyzing a nation-wide database. We searched the Center for Cancer Genomics and Advanced Therapeutics database and downloaded clinical and genomic data from 3,240 lung cancer cases registered from June 2019 to August 2023. Patients undergoing tissue tests and plasma tests were analyzed separately. NSCLC with previously known driver mutations and those without were further analyzed separately. All 3,240 lung cancer patients were analyzed for the presence of germline findings. We found that 25 % of patients who had negative companion diagnostic results tested positive for driver oncogene mutations with indications for approved inhibitors when they underwent tissue CGP tests. Tissue CGP tests had lower detection rates for gene fusions compared with gene mutations (93 % for mutations and 73 % for fusions, p