National clinical study

PRELUCA: Circulating tumor DNA guided treatment-monitoring in advanced lung cancer - a randomized interventional study

Lung cancer is the leading cause of cancer-related death worldwide with Non-Small Cell Lung Cancer (NSCLC) being the most common subtype. A randomized interventional multicenter study will be performed, investigating the true clinical potential of liquid biopsy compared to standard monitoring by radiological scans.

ClincalTrials.gov: NCT05889247

The project received funding in 2023

Abstract

Lung cancer is the leading cause of cancer-related death worldwide with Non-Small Cell Lung Cancer (NSCLC) being the most common subtype. Performance status deterioration due to progressive symptoms and toxicity by treatments are major challenges in managing advanced NSCLC patients. Moreover, standard treatment monitoring by radiologic scans is often imprecise. This technology has limited sensitivity as only a visible increase or decrease in tumor mass can be evaluated, making interpretation challenging and conclusions of whether patients benefit from treatment indefinite. Interpretation of radiologic scans has been further challenged after implementation of immunotherapy, causing immunotherapy-induced recruitment of immune cells resembling increment in tumor size, called “pseudo-progression.” More sensitive methods are highly needed to reduce ineffective treatments and needless toxicity. Liquid biopsy has the potential to overcome these challenges by measuring molecular changes with high precision in a dynamic manner. Recent studies have demonstrated its promising potential as a biomarker predictive of treatment efficacy and overall survival. In our recent real-life study, we found that ctDNA measurements could reduce 33% of likely inefficient treatments and clarify 79% of non-conclusive CT-scans, highlighting the clinical potential.

A randomized interventional multicenter study will be performed, investigating the true clinical potential of liquid biopsy compared to standard monitoring by radiological scans. A total of 350 patients with advanced NSCLC will be included in the study from three Departments of Clinical Oncology. Liquid biopsy monitoring comprises longitudinal digital droplet PCR analyses of selected mutations detected by TSO 500 HT gene panel sequencing of diagnostic tissue and plasma samples. Simultaneously, ctDNA methylation analyses will be performed as an explorative part of the study in order to compare these different methodologies.

In the interventional arm, liquid biopsy monitoring will be the basis for treatment discontinuation before the standard two years of immunotherapy in patients reaching a complete molecular response in plasma, characterizing the long-term responders of immunotherapy. Thus clarifying the question if treatment duration can be reduced for the benefit of patients and health cost.

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