Work

Circulating tumour DNA as a predictive biomarker for tumour response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer

Year: 2025

Type: article

Abstract: INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of advanced non-small cell lung cancer (NSCLC). Quantitative monitoring of disease burden may prove predictive in these cases. We hypothesised that serial ctDNA molecular response assessment may be predictive of response to nivolumab. MATERIALS AND METHODS: 44 NSCLC patients who received nivolumab were included. All the patients underwent response assessment by RECIST every four cycles. Peripheral blood samples were obtained at baseline and after four cycles of therapy, and the quantification of ctDNA was performed by qubit dsDNA HS assay. A variant allele fraction (VAF) of >0.3% was considered to be used for tracking. A cut-off change of 50% in VAF and ctDNA was considered for molecular response. Radiological evaluations were performed at baseline and every four cycles as per RECIST 1.1 criteria. RESULTS: The median ctDNA concentration was higher in patients with time to progression (TTP) of <4 months (P = 0.05). Detectable alterations with >0.3% VAF were detected in 31 patients, and a molecular response of >50% was observed in patients with PR, stable disease (SD) and two patients with PD. The patients with <50%molecular response had a median PFS of 3.9 months vs. those with >50% had a median of 5.8 months (P = 0.06). A cut of 0.3 ng/microlitre baseline ctDNA concentration was predictive of PFS. CONCLUSION: This is an initial experience from India using liquid biopsy next-generation sequencing (NGS) for dynamic monitoring in immunotherapy-treated patients. A 50% cut-off for response as well as a baseline ctDNA 0f 0.3 ng/microlitre showed a trend for better PFS in these patients. This study highlights the need for serial monitoring. To our knowledge, this is among the first real-world Indian studies validating serial NGS-based ctDNA monitoring in immunotherapy-treated NSCLC. It demonstrates feasibility, predictive value, and real-world applicability in a lower-middle-income context.

Source: Lung India

DOI: 10.4103/lungindia.lungindia_127_25