Detectable ctDNA during and after consolidation treatment with durvalumab is associated with shorter progression-free survival in patients with unresectable stage III NSCLC, researchers report.

The data suggest that ctDNA-monitoring could identify patients at high risk of disease relapse after standard chemoradiotherapy and immunotherapy, and thus help to refine follow-up strategies.

Currently, post-treatment surveillance relies on CT imaging and clinical assessment, and there is no routine molecular monitoring strategy for detecting residual disease or determining relapse risk.

In the prospective, multicentre study, published in Journal of Thoracic Oncology [link here], patients with detectable ctDNA during or after durvalumab experienced significantly worse outcomes than those with undetectable ctDNA.

“Detectable ctDNA during and after durvalumab was associated with markedly shorter PFS in unresectable stage III NSCLC,” the authors said.

“Serial ctDNA-based MRD assessment may help identify patients at high risk of relapse who could benefit from alternative or intensified treatment strategies, ideally within prospective clinical trials.”

For the analysis, the team collected samples from patients with unresectable stage III NSCLC at screening, after chemoradiotherapy, at predefined timepoints during durvalumab, and during post-treatment follow-up.

Using a tumour-agnostic, ctDNA MRD assay personalised to each patient’s molecular profile, samples were classified as either ctDNA detected (MRD-positive) or not detected (MRD-negative).

Among a total of 659 plasma samples from 84 patients, key findings were that:

• detectable ctDNA before the seventh cycle of durvalumab and at three months after treatment completion was strongly associated with inferior PFS, with hazard ratios (HR) of 2.45 (p=0.013) and 5.37 (p<0.001), respectively; and
• ctDNA detection immediately after chemoradiotherapy but prior to durvalumab was not associated with PFS, whereas detection during or after durvalumab was strongly prognostic.

Also, in a multivariable model incorporating all post-CRT samples, detectable ctDNA was linked with a nearly threefold higher risk of disease progression (HR: 2.95, p < 0.001), according to the paper.

However, the researchers also stressed that the findings remain exploratory, and that prospective biomarker-driven trials will be necessary to determine how ctDNA should inform clinical decision-making.

If validated, a ctDNA-based MRD surveillance strategy, with serial ctDNA testing over the course of treatment, could complement conventional follow-up and accelerate intervention for those at high risk of relapse, they said.