Liquid Biopsy for EGFR Mutation Analysis in Advanced Non-Small-Cell Lung Cancer Patients: Thoughts Drawn from a Real-Life Experience.

Paola Ulivi,Paola Cravero,Daniele Calistri,Matteo Canale,Alice Rossi,Lucio Crinò,Ilaria Priano,Elisa Chiadini,Elisabetta Petracci,Giuseppe Bronte,Laura Capelli,Angelo Delmonte

doi:10.3390/biomedicines9101299

Abstract

Background: Liquid biopsy analysis for EGFR detection in cell-free DNA (cfDNA) from NSCLC patients has become routine. The aim of this study was to explore its applicability in clinical practice. Methods: We collected data of EGFR-mutated NSCLC patients with liquid biopsy analysis. Data included test timing, concomitant tissue re-biopsy, therapy change, histology, stage, smoking habits, gender and age. All analyses were performed via a real-time PCR method to analyze EGFR mutations at exons 18, 19, 20 and 21. Variant allele frequency was performed for patients with available sequential EGFR mutation analysis in cfDNA. Overall survival was analyzed through the Kaplan–Meier method. We designed flow charts to show the real-life application of liquid biopsy. Results: We found that liquid biopsy is used in treatment-naïve patients as an alternative to EGFR detection in tumor tissue, and in patients with positive or negative EGFR from tumor biopsy. The majority of liquid biopsy analyses were performed in NSCLC patients who were disease progressive during TKI therapy. The presence of EGFR mutation in cfDNA was associated with a worse prognosis. In two patients, VAF of EGFR mutations in cfDNA was concordant with tumor volume changes. Conclusion: These findings suggest that liquid biopsy for EGFR detection can continue to be useful.

Highlights

Non-small cell lung cancer (NSCLC) represents about 85% of lung cancers, and the predominant histotype is adenocarcinoma [1]
Through next-generation sequencing (NGS)-based cell-free DNA (cfDNA) analysis performed at that time, we found that the epidermal growth factor receptor (EGFR) L858R mutation of exon 21 was not associated with T790M
We evaluated the applicability of liquid biopsy analysis for EGFR detection in EGFR-mutated NSCLC patients

Summary

Introduction

Non-small cell lung cancer (NSCLC) represents about 85% of lung cancers, and the predominant histotype is adenocarcinoma [1]. Mutations in the epidermal growth factor receptor (EGFR) are present in around 15% of adenocarcinomas and represent the target for first-, second- and third-generation tyrosine kinase inhibitors (TKIs), all usable in clinical practice [2,3,4,5]. The detection of EGFR mutations in tumor-tissue samples is considered the gold standard for molecular diagnostics. There are some circumstances where tumor-tissue analysis is very difficult for several reasons, e.g., insufficient tumor material available at diagnosis, only bone biopsy available with difficulties performing. Biomedicines 2021, 9, 1299 molecular analysis or patient clinical conditions may not permit invasive procedures to obtain the biological material. Patients treated with first- (Gefitinib or Erlotinib) or second-generation (Afatinib) TKIs progress with the development of EGFR T790M mutation, which represents a marker of sensitivity to treatment with the third-generation

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