Journal Article

Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non‐small‐cell lung cancer treated with pembrolizumab

Rodríguez‐Casanova, Aitor, Mondelo‐Macía, Patricia, Anido, Urbano, Díaz‐Lagares, Ángel, Lago‐Lestón, Ramón Manuel, Aguín, Santiago, Abdulkader, Ihab, Díaz‐Peña, Roberto, Abalo, Alicia, Muinelo‐Romay, Laura, López‐López, Rafael, Sánchez‐Ares, María, García‐González, Jorge, León‐Mateos, Luis

2021

Overview

Immune checkpoint inhibitors, such as pembrolizumab, are revolutionizing therapeutic strategies for different cancer types, including non‐small‐cell lung cancer (NSCLC). However, only a subset of patients benefits from this therapy, and new biomarkers are needed to select better candidates. In this study, we explored the value of liquid biopsy analyses, including circulating free DNA (cfDNA) and circulating tumour cells (CTCs), as a prognostic or predictive tool to guide pembrolizumab therapy. For this purpose, a total of 109 blood samples were collected from 50 patients with advanced NSCLC prior to treatment onset and at 6 and 12 weeks after the initiation of pembrolizumab. Plasma cfDNA was measured using hTERT quantitative PCR assay. The CTC levels at baseline were also analysed using two enrichment technologies (CellSearch® and Parsortix systems) to evaluate the efficacy of both approaches at detecting the presence of programmed cell death ligand 1 on CTCs. Notably, patients with high baseline hTERT cfDNA levels had significantly shorter progression‐free survival (PFS) and overall survival (OS) than those with low baseline levels. Moreover, patients with unfavourable changes in the hTERT cfDNA levels from baseline to 12 weeks showed a higher risk of disease progression. Additionally, patients in whom CTCs were detected using the CellSearch® system had significantly shorter PFS and OS than patients who had no CTCs. Finally, multivariate regression analyses confirmed the value of the combination of CTCs and cfDNA levels as an early independent predictor of disease progression, identifying a subgroup of patients who were negative for CTCs, who presented low levels of cfDNA and who particularly benefited from the treatment. In the present work, we demonstrated that liquid biopsy, through the combinatory analyses of circulating free DNA (cfDNA) and circulating tumour cells and the monitoring of cfDNA during the treatment, could help to select advanced non‐small‐cell lung cancer patients who will benefit from pembrolizumab treatment as first line, providing a promising non‐invasive strategy for improving the clinical management of this tumour.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Antibodies, Monoclonal, Humanized / Apoptosis / Biomarkers / Biomarkers, Tumor / Biopsy / Calibration / Cancer / Cancer therapies / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - pathology / Care and treatment / Cell death / Cell-Free Nucleic Acids / cfDNA / CTCs / Deoxyribonucleic acid / Development and progression / DNA / FDA approval / Genetic aspects / Humans / Immune checkpoint inhibitors / Immunotherapy / Ligands / Lung cancer / Lung cancer, Non-small cell / Lung cancer, Small cell / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Metastases / Metastasis / Neoplastic Cells, Circulating - pathology / Non-small cell lung carcinoma / NSCLC / Patients / PD‐L1 / Pembrolizumab / Proteins / Risk assessment / Telomerase reverse transcriptase / Tumors