Cell-free DNA NGS detects common and novel ALK fusions in the plasma of lung cancer patients
Agilent Technologies Inc. (NYSE: A) today announced the publication of a paper in the journal Lung Cancer, titled "Clinical Utility of Next-Generation Sequencing-Based ctDNA Testing for Common and Novel ALK Fusions". The study, jointly published by Resolution Bioscience (now a part of Agilent) and Memorial Sloan Kettering Cancer Center (MSK), describes the use of plasma ctDNA NGS to detect novel anaplastic lymphoma kinase (ALK) fusions, and to serially monitor the development of mechanisms of resistance in response to targeted therapy.
The development of drugs that target ALK fusions represented a crucial milestone in the advent of precision oncology; ALK fusions have been reported in approximately 5% of patients with NSCLC1. The use of next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) to detect ALK fusions is an emerging alternative to tissue-based methodologies such as fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and tissue-based NGS. Compared to tissue tests, liquid biopsy has the advantage of not requiring an invasive tissue biopsy, having a significantly shorter turnaround time, and allowing for serial testing that can track tumor response and detect tumor evolution2,3.
Katharine Knobil, M.D., chief medical officer at Agilent Technologies, discussed the importance of the findings. “A number of targeted drugs now exist for the treatment of patients with ALK fusions. However, detecting ALK fusions using liquid biopsy is challenging,” Knobil said. “This paper demonstrates the capability of the Resolution platform to detect ALK fusions from the blood of patients with NSCLC in a non-invasive and timely manner. Most importantly, it was able to demonstrate clinical benefit by guiding patients to positive clinical responses.”
Bob Li, MD, PhD, MPH, co-director of the Thoracic Liquid Biopsy Program at MSK, remarked, “As a continuation of our multiyear collaboration with Resolution Bioscience, this study provides further evidence for the clinical utility of liquid biopsy, here with a focus on ALK fusion detection, for which there is limited data. In addition to detecting common EML4-ALK fusions, liquid biopsy was also able to detect resistance mechanisms like MET amplifications and discover novel fusion partners, including a patient with a PON1-ALK fusion. This patient was treated with alectinib based on the liquid biopsy result and had a durable response.”
Resolution Bioscience is dedicated to developing a highly sensitive, non-invasive liquid biopsy platform that improves cancer diagnostics and monitoring for patients around the world. The company has developed core technology for circulating cell-free DNA NGS analysis. Resolution Bioscience’s Liquid Biopsy assays are powered by the company’s cell-free DNA (cfDNA) analysis platform, which includes targeted capture next-generation sequencing (NGS) biochemistry and tightly coupled, cloud-based bioinformatics. The Resolution Bioscience homologous recombination deficiency (HRD) assay has received Breakthrough Device Designation from the U.S. Food and Drug Administration.
This study reinforces Agilent's commitment to partnering with leaders in clinical oncology through the continued development and application of key Resolution Bioscience diagnostics tools to provide valuable solutions that drive positive clinical responses.
- J.P. Koivunen, C. Mermel, K. Zejnullahu, C. Murphy, E. Lifshits, A.J. Holmes, H.G. Choi, J. Kim, D. Chiang, R. Thomas, J. Lee, W.G. Richards, D.J. Sugarbaker, C. Ducko, N. Lindeman, J.P. Marcoux, J.A. Engelman, N.S. Gray, C. Lee, M. Meyerson, P.A. Janne, EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer, Clin Cancer Res 14(13) (2008) 4275-83.
- J.K. Sabari, M. Offin, D. Stephens, A. Ni, A. Lee, N. Pavlakis, S. Clarke, C.I. Diakos, S. Datta, N. Tandon, A. Martinez, M.L. Myers, A. Makhnin, Y. Leger, H.A. Yu, P.K. Paik, J.E. Chaft, M.G. Kris, J.O. Jeon, L.A. Borsu, M. Ladanyi, M.E. Arcila, J. Hernandez, S. Henderson, T. Shaffer, K. Garg, D. DiPasquo, C.K. Raymond, L.P. Lim, M. Li, M.D. Hellmann, A. Drilon, G.J. Riely, V.W. Rusch, D.R. Jones, A. Rimner, C.M. Rudin, J.M. Isbell, B.T. Li, A prospective study of circulating tumor DNA to guide matched targeted therapy in lung cancers, J Natl Cancer Inst (2018).
- C. Lin, X. Shi, S. Yang, J. Zhao, Q. He, Y. Jin, X. Yu, Comparison of ALK detection by FISH, IHC and NGS to predict benefit from crizotinib in advanced non-small-cell lung cancer, Lung Cancer 131 (2019) 62-68.
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