Plasma-based next generation sequencing in advanced non-small cell lung cancer (NSCLC): Significance in diagnosis and treatment.
Authors: Cherng-Horng Wu, Xia Wu, Xiao Hu, Alice Kennedy, Lori H. Pai
Journal: Journal of Clinical Oncology (2025)

e20635 Background: Next generation sequencing (NGS) is recommended in the evaluation of advanced NSCLC prior to treatment. However, up to 20% of tissue biopsies are insufficient to run molecular testing for all 9 FDA recommended biomarkers. Our study aims to assess the role of plasma-based NGS in the diagnosis and treatment of metastatic NSCLC with real-world data enriched with Asian Americans. Methods: A retrospective single-center study was conducted to examine the use of plasma-based NGS in patients with treatment naïve metastatic lung adenocarcinoma from 1/1/2015 to 12/31/2023. For patients that received both tissue and plasma-based NGS concordance was calculated. Chi-square/Fischer's exact tests were used to compare the difference in actionable mutation seen on plasma based-NGS by race, smoking status, and gender. Results: 91 patients were included for final analysis, with majority being Asian (54%) or white (37%). 49% were males and 36% were nonsmokers. Analysis showed that there was high concordance among the 9 FDA biomarker in plasma-based and tissue NGS. On plasma-based NGS, there was a higher chance of detecting an EGFR actionable mutation in Asians compared to Whites (P = .004), and nonsmokers compared to smokers (P=0.017). In addition, a small number of patients (Table 1) had an actionable mutation on plasma-based NGS but not on tissue NGS despite sufficient tissue for analysis. Conclusions: Our study is unique given our ability to do direct race comparisons of patients who received plasma-based NGS and detailed analysis of their treatment history. A subset of patients derived benefit from plasma-based NGS directed therapy. These patients experienced varying degrees of benefit. For this subset of patients with EGFR mutation, treatment PFS and OS was shorter than expected for some but for others similar to what was published in FLAURA. Plasma-based NGS should be considered if an actionable mutation is not detected in Asians or nonsmokers even if there is sufficient tissue for NGS. Outcomes in patients who were treated based on results of plasma-based NGS alone. Age Sex Actionable mutation detected on plasma-based NGS alone Was tissue biopsy done Did tissue biopsy detect an actionable mutation 1 st line treatment PFS (days) OS (days) 98 F EGFR (Exon 19 deletion) No N/A Erlotinib N/A 1295 69 M EGFR (G719A) Yes No Osimertinib 175 1046 87 F EGFR E746_A750del Yes No Osimertinib 195 378 76 F EGFR E746_T751delinsV Yes QNS Osimertinib 50 NR 76 F EGFR exon 20 insertion H773_V774dup (0.08%) Yes No Carboplatin, Pemetrexed, Pembrolizumab 212 NR 54 M ALK rearrangement Yes No Carboplatin and pemetrexed N/A 145 66 M KRAS G12c Yes No Palliative N/A Deceased 66 F KRAS G12c Yes QNS Palliative NA Deceased 63 M ROS1 rearrangement Yes QNS Carbozatinib 312 791 75 M MET_Exon 14 skipping mutation Yes QNS Capmatinib N/A 40 QNS= Quantity not sufficient; N/A= Not applicable; NR= Not reached; QNS=quantity not sufficient.