2023 World Conference on Lung Cancer (Posters)-P1.23. Circulating Tumour DNA as a Predictive Biomarker for Tumour Response and Prolonged Clinical Benefit with Nivolumab in NSCLC

P1.23. Circulating Tumour DNA as a Predictive Biomarker for Tumour Response and Prolonged Clinical Benefit with Nivolumab in NSCLC - PDF(Slides)

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This study examines the use of circulating tumour DNA (ctDNA) as a predictive biomarker for tumour response and prolonged clinical benefit with the immunotherapy drug Nivolumab in non-small cell lung cancer (NSCLC). The researchers conducted a prospective, single-center study in India to assess the dynamic changes in ctDNA and molecular response to Nivolumab treatment.<br /><br />The study found that the median ctDNA concentration was higher in patients with a time to progression (TTP) of less than 4 months compared to those with a TTP of 4 months or more. Detectable alterations with a variant allele frequency (VAF) of 0.3% were found in 32 patients. A molecular response of 50% was observed in patients with partial response, stable disease, and 2 patients with progressive disease. Patients with a molecular response of 50% or more had a median progression-free survival (PFS) of 5.5 months, compared to those with a response of less than 50% who had a median PFS of 3.9 months.<br /><br />The study also found that a baseline ctDNA concentration of 0.3ng/microliter was predictive of PFS. Furthermore, the level of ctDNA at 4 weeks was predictive of progression in patients showing initial unconfirmed progressive disease at their first evaluation.<br /><br />The researchers used liquid biopsy and next-generation sequencing (NGS) to analyze ctDNA. They noted that quantitative monitoring with absolute numbers of copies is possible using digital droplet PCR (ddPCR) or NGS. However, they highlighted that ddPCR suffers from user-dependent variabilities, while NGS can detect even newer subclones.<br /><br />The study emphasizes the need for serial monitoring of ctDNA, which may serve as an early predictor of response compared to radiologic evaluation. The researchers suggest that the findings from this study could help in the development of biomarkers and monitoring strategies for immunotherapy-treated patients.<br /><br />It is important to note that the study had limitations, including a small sample size, the use of second-line Nivolumab, and potential contamination by CHIP mutations. The researchers also mentioned that the limited sensitivity of fusion detection may have missed some new alterations.<br /><br />The study was supported by an educational research grant from Bristol Meyer Squibb.

Asset Subtitle

Ullas Batra

Meta Tag

Speaker Ullas Batra

Topic Pathology & Biomarkers: Liquid Based Biomarkers

Keywords

ctDNA

predictive biomarker

Nivolumab

NSCLC

molecular response

progression-free survival

liquid biopsy

NGS

biomarkers

monitoring strategies