EGFR Detection by Liquid Biopsy: Ripe for Clinical Usage

Abstract

Introduction: With the International Association for the Study of Lung Cancer (IASLC) recommendations promoting liquid biopsy as a primary detection tool, a new era of research has begun. The authors aimed to study the concordance of plasma genotyping platforms against the tissue gold standard. Methods: 184 patients with non-small cell lung cancer underwent EGFR genotyping using Cobas, droplet digital polymerase chain reaction (ddPCR) and Therascreen assays from 2019–2020. Results: Of 184 cases, 70 were positive by Cobas, 51 by ddPCR and 69 by Therascreen. The sensitivity of Cobas was 97.1% and the sensitivity of ddPCR was 71%. Receiver operating characteristic analysis showed an area under the curve of 0.977 for Cobas and 0.846 for ddPCR. Conclusion: In line with the FLAURA trial of osimertinib making its way to first-line and given the IASLC recommendations, it is important to understand the attributes of these tests to initiate appropriate treatment.

Lay abstract

Lung cancer is one of the most common malignancies and has been known to have a dismal outcome. However, owing to evolution in the knowledge of disease biology and processes, many molecules have been discovered that can be used in targeted therapy. To institute this modality of treatment, detection of alterations in these specific molecules, namely: EGFR, ALK, ROS1, RET, MET, KRAS G12C, BRAF V600E, NTRK1, NTRK2, NTRK3 and ERBB2 is necessary. This has traditionally been done using single-gene assays, which require more tissue. This is a major limitation in cases of non-small cell lung carcinoma, as the biopsies are small. Hence, new technologies like next-generation sequencing have emerged that offer a one-stop solution for these cases. In cases where tissue is very scant, the use of peripheral blood has now been recommended by international guidelines for primary detection of these molecular alterations. This article describes the concordance of tissue-based detection and blood-based detection using three different assays, for the detection of EGFR alterations. Although promising results were obtained largely for blood-based assays, liquid and tissue biopsies are complementary.

Author contributions

U Batra: Conceptualization, reviewing of results and manuscript. S Nathany, M Sharma: Data collection and tabulation, statistics and writing the manuscript. H Singh and S Dhanda: Sample collection from patients, consenting and wetlab procedures. P Jain and A Jain: Clinical evaluation and patient consent. A Mehta: Reporting of laboratory results, supervision.

Acknowledgments

We acknowledge the efforts of the management, doctors and staff of RGCI for their constant support and dedication for easy implementation and facilitation of this project.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study has been carried out in accordance with Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. The study has been approved by the Institutional Review Board (Res/SCM/45/2021/50).

Data sharing statement

The authors declare that the results reported here are from an original research study and the individual data of patients will not be made publicly available.

Additional information

Funding

We acknowledge the efforts of the management, doctors and staff of RGCI for their constant support and dedication for easy implementation and facilitation of this project