DART Trial Assesses Relationship Between ctDNA and Outcomes in Unresectable NSCLC

Circulating tumor DNA (ctDNA) may be a potential biomarker to identify high-risk patients with unresectable stage III non–small cell lung cancer (NSCLC) who could benefit from tailored interventions, according to findings from the first minimal residual disease (MRD) analysis of the DART trial.

In the DART study, all patients (n=86) received two cycles of platinum-doublet chemotherapy concomitant with radiotherapy to a total dose of 60 to 66 Gy, followed by durvalumab. Plasma samples were collected at baseline, 1 month after chemoradiotherapy (CRT), and at predefined times during durvalumab treatment. A novel tumor-agnostic ctDNA MRD assay was used to analyze the samples.

“Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection has shown promise as a tool for risk-adaptive and personalized treatment strategies in resectable NSCLC but is still underexplored as a biomarker in patients with stage III NSCLC treated with CRT and consolidative durvalumab,” said the researchers, who were led by Henrik Horndalsveen, MD, Oslo University Hospital, Oslo, Norway.

Results of the first MRD analysis, which were presented at the 2025 American Society of Clinical Oncology Annual Meeting, included 138 plasma samples from 20 patients. DNA from selected coding regions in 293 genes was studied to classify plasma samples as positive (ctDNA detected) or negative (ctDNA not detected).

“Detection of ctDNA during consolidative durvalumab after CRT using a novel tumor-agnostic MRD assay was associated with inferior outcomes,” the researchers said.

At baseline, the ctDNA detection rate was 91.8% in the entire study population and 73.7% in the 20 patients with completed longitudinal MRD analyses. Detectable ctDNA at baseline varied according to histology and stage but wasn’t associated with progression-free survival (PFS).

Furthermore, within the first 4 months after CRT, nine patients had detectable ctDNA in at least one plasma sample, which was significantly associated with shorter PFS compared with patients who didn’t have detectable ctDNA at that time point. However, the researchers observed no association with shorter PFS in patients with detectable ctDNA at 1 month after CRT.

Detectable ctDNA appeared to show worse overall survival (OS). Patients who were ctDNA positive during the first 4 months after CRT had significantly increased odds of death within 24 months, according to preliminary OS data.