Early ctDNA Decrease Predicts Immunotherapy Response in Advanced Non-Small Cell Lung Cancer
According to results from a prospective study, early decreases in circulating tumor DNA (ctDNA) after initiating pembrolizumab with or without chemotherapy can predict response to treatment in patients with advanced non-small cell lung cancer (NSCLC).
These findings were presented by Diego Enrico, MD, Alexander Fleming Cancer Institute, Buenos Aires, Argentina, at the 2025 International Society of Liquid Biopsy (ISLB) Annual Meeting in Orlando, Florida.
In this study, researchers enrolled 13 patients without EGFR, ALK, ROS1, or BRAF alterations receiving first-line pembrolizumab either with (n = 4) or without platinum-based chemotherapy (n = 9). Plasma samples were collected at baseline, followed by once every 6 weeks. ctDNA levels were quantified using the Signatera tumor-informed minimal residual disease (MRD) assay and expressed as mean tumor molecules (MTM)/mL. Early ctDNA changes were correlated with radiologic response and clinical outcomes.
At analysis, median baseline ctDNA was 13.28 MTM/mL which decreased to 5.66 MTM/mL at first follow-up (median 42 days). Median ctDNA change was −100% among patients who achieved a partial response (n = 10), −51.3% among patients with stable disease (n = 2), and +78.5% for the single patient with progressive disease (P = .006). Early ctDNA dynamics showed a strong correlation with RECIST radiologic response (R=0.81, P < 0.001). The objective response rate among those patients with a decline in ctDNA from baseline to the first on-treatment sample was 91%, compared to 0% in those patients who did not experience a decline in ctDNA from baseline to the first on-treatment sample (P = .038).
“Early ctDNA reduction after initiation of immunotherapy ± chemotherapy in advanced NSCLC correlates with radiologic and clinical outcomes, supporting its role as an early biomarker of response or resistance,” concluded Dr Enrico.
Source:
Enrico D. Tumor-informed circulating tumor DNA (ctDNA) in advanced NSCLC treated with pembrolizumab ± chemotherapy. Presented at the 2025 ISLB Annual Meeting. November 1-3, 2025; Orlando, Florida. PP.14
