A Large-Scale Prospective Concordance Study of Plasma- and Tissue-Based Next-Generation Targeted Sequencing for Advanced Non–Small Cell Lung Cancer (LC-SCRUM-Liquid)

Author:

Sugimoto Akira1ORCID,Matsumoto Shingo1ORCID,Udagawa Hibiki1ORCID,Itotani Ryo1ORCID,Usui Yuko1ORCID,Umemura Shigeki1ORCID,Nishino Kazumi2ORCID,Nakachi Ichiro3ORCID,Kuyama Shoichi4ORCID,Daga Haruko5ORCID,Hara Satoshi6ORCID,Miyamoto Shingo7ORCID,Kato Terufumi8ORCID,Sakakibara-Konishi Jun9ORCID,Tabata Eriko10ORCID,Nakagawa Taku11ORCID,Kawaguchi Tomoya12ORCID,Sakai Tetsuya1ORCID,Shibata Yuji1ORCID,Izumi Hiroki1ORCID,Nosaki Kaname1ORCID,Zenke Yoshitaka1ORCID,Yoh Kiyotaka1ORCID,Goto Koichi1ORCID

Affiliation:

1. 1Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

2. 2Department of Thoracic Oncology, Osaka International Cancer Institute, Chuo-ku, Osaka, Japan.

3. 3Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan.

4. 4Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan.

5. 5Department of Medical Oncology, Osaka City General Hospital, Miyakojima-ku, Osaka, Japan.

6. 6Department of Respiratory Medicine, Itami City Hospital, Itami, Hyogo, Japan.

7. 7Department of Medical Oncology, Japanese Red Cross Medical Center, Shibuya-ku, Tokyo, Japan.

8. 8Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.

9. 9Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

10. 10Department of Respiratory Medicine, Ikeda City Hospital, Ikeda, Osaka, Japan.

11. 11Department of Thoracic Surgery, Omagari Kosei Medical Center, Daisen, Akita, Japan.

12. 12Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University, Abeno-ku, Osaka, Japan.

Abstract

Abstract Purpose: We evaluated plasma cell-free DNA (cfDNA) and tissue-based sequencing concordance for comprehensive oncogenic driver detection in non–small cell lung cancer (NSCLC) using a large-scale prospective screening cohort (LC-SCRUM-Liquid). Experimental Design: Blood samples were prospectively collected within 4 weeks of corresponding tumor tissue sampling from patients with advanced NSCLC to investigate plasma cfDNA sequencing concordance for alterations in 8 oncogenes (EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1) compared with tissue-based next-generation targeted sequencing. Results: Paired blood and tissue samples were obtained in 1,062/1,112 enrolled patients with NSCLC. Oncogenic alteration was detected by plasma cfDNA sequencing and tissue assay in 455 (42.8%) and 537 (50.5%) patients, respectively. The positive percent agreement of plasma cfDNA sequencing compared with tissue DNA and RNA assays were 77% (EGFR, 78%; KRAS, 75%; BRAF, 85%; HER2, 72%) and 47% (ALK, 46%; RET, 57%; ROS1, 18%; MET, 66%), respectively. Oncogenic drivers were positive for plasma cfDNA and negative for tissue due to unsuccessful genomic analysis from poor-quality tissue samples (70%), and were negative for plasma cfDNA and positive for tissue due to low sensitivity of cfDNA analysis (61%). In patients with positive oncogenic drivers by plasma cfDNA sequencing but negative by tissue assay, the response rate of genotype-matched therapy was 85% and median progression-free survival was 12.7 months. Conclusions: Plasma cfDNA sequencing in patients with advanced NSCLC showed relatively high sensitivity for detecting gene mutations but low sensitivity for gene fusions and MET exon 14 skipping. This may be an alternative only when tissue assay is unavailable due to insufficient DNA and RNA. See related commentary by Jacobsen Skanderup et al., p. 1381

Funder

National Cancer Center Japan

Japan Agency for Medical Research and Development

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Reference16 articles.

1. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs;Kris;JAMA,2014

2. Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in non–small cell lung cancer;Liu;Genes Chromosomes Cancer,2018

3. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non–small cell lung cancer;Leighl;Clin Cancer Res,2019

4. Biomarker discovery and outcomes for comprehensive cell-free circulating tumor DNA versus standard-of-care tissue testing in advanced non–small cell lung cancer;Palmero;JCO Precision Oncology,2021

5. Clinical outcomes in non–small cell lung cancer patients treated with EGFR—tyrosine kinase inhibitors and other targeted therapies based on tumor versus plasma genomic profiling;Tran;JCO Precis Oncol,2021

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