Persistent Oncogenic Drivers on Serial Liquid Biopsies Linked to Shorter Progression-Free Survival in TKI-Treated Non-Small Cell Lung Cancer
Results from a retrospective analysis show that persistence of oncogenic driver mutations detected through serial liquid biopsies is linked to markedly shorter progression-free survival (PFS) among patients with non-small cell lung cancer (NSCLC) receiving tyrosine kinase inhibitor (TKI) therapy.
These findings were presented by Rodrigo Paredes, MD, Mount Sinai Health, New York, New York, at the 2025 International Society of Liquid Biopsy (ISLB) Annual Meeting in Orlando, Florida.
In this study, researchers collected data from 23 patients who underwent liquid biopsies at baseline and radiographic progression. Mutations were classified as either oncogenic drivers or tumor suppressor alterations. For each gene class, patients were categorized as having kept, lost, or gained mutations between baseline and progression. The primary end point was PFS.
At analysis, 14 patients retained their driver mutation, 9 lost their driver mutation, and 2 gained a new driver mutation. Median PFS was 7.2 months in patients with persistent drivers and 26 months in patients who lost drivers (P = .03). Driver persistence was associated with shorter PFS (hazard ratio [HR]. 2.76; 95% confidence interval [CI], 1.09 to 7; P = .033) and this association was strengthened when analysis was limited to patients with a baseline driver (HR 3.25; 95% CI, 1.22 to 8.70; P = .019). Tumor suppressor dynamics were not associated with PFS (HR 2.28; 95% CI, 0.65 to 8.02). PFS was 7.1 in patients with increasing driver variant allele frequency and 20.7 months in patients with decreasing variant allele frequency (P = .15).
“Persistence of oncogenic drivers in serial liquid biopsies was concordant with a significantly shorter PFS in TKI treated NSCLC,” concluded Dr Paredes. “These findings could support the clinical utility of serial liquid biopsy to monitor resistance and guide therapeutic strategies in NSCLC.”
Source:
Paredes R. Oncogenic driver persistence in liquid biopsies as predictor outcomes in TKI treated non-small cell lung cancer. Presented at the 2025 ISLB Annual Meeting. November 1-3, 2025; Orlando, Florida. PP.37
