1436P - Prospective study utilizing ctDNA genome-wide copy number variations for longitudinal monitoring of patients with advanced non-small cell lung cancer

Background

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. While the development of targeted therapies has led to significant improvements in NSCLC patient outcomes, resistance can develop over time. Hence, there is need for reliable methods to monitor treatment response and identify tumor relapse. Circulating tumor DNA (ctDNA) in plasma has emerged as a promising biomarker for NSCLC, which can be used for longitudinal tumor monitoring.

Methods

The study recruited 69 patients with advanced NSCLC and collected their blood samples at the baseline. Patients were treated with targeted therapies tailored to their biomarker profiles. Blood samples were collected approximately every three months until disease progression, and were delivered to a central laboratory for ctDNA analysis. The study applied PredicineSCORE, a low-pass whole-genome sequencing (LP-WGS) assay, to monitor disease progression during treatment.

Results

In this ongoing study, baseline blood samples from 69 enrolled patients were tested, of whom 12 patients had longitudinal blood samples tested at multiple follow-up time points. Using the ctDNA assay, gene copy variants related to NSCLC were detected at baseline, including copy gain of EGFR (n=11), PIK3CA (n=10), KRAS (n=9), AKT3 (n=8), AKT2 (n=7), ERBB2 (n=7), and copy loss of TP53 (n=8), FAT1 (n=7), BAP1 (n=7), BRCA2 (n=7), and RB1 (n=6). The assay also measured the genome-wide copy number burden (CNB) levels in plasma samples as an approach for treatment monitoring. Among the 12 patients whose longitudinal samples were tested, 7 were observed to have a CNB decrease during treatment, which was correlated with their clinical response. Notably, the study also found that 2 patients had an increase in CNB, preceding the clinical detection of disease progression.

Conclusions

Next-generation sequencing (NGS)-based ctDNA tests using plasma have demonstrated remarkable molecular profiling capabilities in advanced NSCLC patients. PredicineSCORE-based LP-WGS assays performed in the study have revealed the copy number burden profiles of NSCLC, which provides potential biomarkers for longitudinal monitoring of treatment response and disease progression.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.