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A large scale prospective concordance study of oncogene driver detection between plasma- and tissue-based NGS analysis in advanced non-small cell lung cancer (NSCLC).

Date

28 Sep 2019

Session

Poster Display session 1

Presenters

Ryo Itotani

Citation

Annals of Oncology (2019) 30 (suppl_5): v602-v660. 10.1093/annonc/mdz260

Authors

R. Itotani1, S. Matsumoto1, H. Udagawa1, K. Nishino2, I. Nakachi3, S. Miyamoto4, S. Hara5, S. Kuyama6, N. Ebi7, Y. Tsubata8, M. Shingyoji9, T. Kato10, Y. Ohe11, K. Nishi12, S. Hashimoto13, K. Goto1

Author affiliations

  • 1 Department Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2 Department Of Thoracic Oncology, Osaka International Cancer Institute, 541-8567 - Oosaka/JP
  • 3 Department Of Respiratory Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya/JP
  • 4 Department Of Medical Oncology, Japanese Red Cross Medical Center, Tokyo/JP
  • 5 Department Of Internal Medicine, Itami City Hospital, 664-8540 - Itami/JP
  • 6 Department Of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center, Iwakuni/JP
  • 7 Department Of Respiratory Oncology, Iizuka Hospital, iizuka/JP
  • 8 Department Of Respiratory Medicine And Medical Oncology, Shimane University Hospital, Izumo/JP
  • 9 Division Of Respirology, Chiba Cancer Center, 260-8717 - Chiba/JP
  • 10 Department Of Thoracic Oncology, Kanagawa Cancer Center, 2410815 - Yokohama/JP
  • 11 Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 12 Department Of Respiratory Medicine, Ishikawa Prefecture Central Hospital, Kanazawa/JP
  • 13 Department Of Respiratory Medicine, Ikeda City Hospital, Ikeda/JP
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Background

Liquid biopsy-based next-generation sequencing (NGS) is clinically useful as a less invasive multi-gene analysis for precision cancer medicine. However, performance of NGS using plasma cell-free DNA (cfDNA) compared to tumor tissue has not been evaluated in a large-scale sample.

Methods

A liquid biopsy study is additionally conducted in the nation-wide lung cancer genome screening project (LC-SCRUM-Japan), targeting 2000 NSCLC patients. Tumor genetic alterations are evaluated by cfDNA- and tissue-based NGS tests. Plasma is collected within 4 weeks of the corresponding tissue biopsy. cfDNA is analyzed using Guardant360 (investigational device exemption version, Guardant Health); tumor tissue is analyzed by Oncomine Comprehensive Assay version 3 (Thermo Fisher Scientific). We assessed the detectability of 8 oncogene drivers: mutations of EGFR, KRAS, BRAF, ERBB2 and MET, and fusions of ALK, RET and ROS1.

Results

As of March 2019, 270 advanced NSCLC patients were enrolled. Median age was 67 (range, 30-87) years, 169 patients (63%) were men, 86 (32%) were nonsmokers, 215 (80%) had adenocarcinoma, 206 (76%) were stage IV, and 224 (83%) received no prior chemotherapy. An oncogene driver was detected in 156 patients (58%) by at least one NGS method, including 138 (51%) in tissue and 107 (40%) in cfDNA. Using the tissue assay as a control, the positive percent agreement (PPA) of gene mutations in the cfDNA assay was 75% (91 of 121), including 74% (53 of 72) for EGFR, 78% (31 of 40) for KRAS, 100% (3 of 3) for BRAF, 75% (3 of 4) for ERBB2 and 50% (1 of 2) for MET. The PPA of gene fusions in the cfDNA assay was 24% (4 of 17), including 33% (2 of 6) for ALK, 33% (2 of 6) for RET and 0% (0 of 5) for ROS1. Of 132 patients in whom no oncogene driver was detected by the tissue assay, 17 had the drivers detected in cfDNA: 8 EGFR, 5 KRAS, 1 BRAF, 1 ERBB2, 1 MET and 1 ALK.

Conclusions

In the cfDNA-based NGS, the detectability of gene mutations was comparable with the previously reported single-gene tests using cfDNA, whereas that of gene fusions was low. The cfDNA-based assay may be useful for patients in whom oncogene driver detection was failed by the tissue-based assay. This study is now ongoing and we will present updated results.

Clinical trial identification

UMIN000030496.

Editorial acknowledgement

Legal entity responsible for the study

National Cancer Center.

Funding

Guardant Health, Merck Serono.

Disclosure

S. Matsumoto: Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Merck Serono. H. Udagawa: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AbbVie; Honoraria (self), Research grant / Funding (self): Daiichisankyo; Honoraria (self), Research grant / Funding (self): MSD; Research grant / Funding (self): AMGEN; Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Chugai Pharma; Honoraria (self): Taiho; Honoraria (self): Ono; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Amco. K. Nishino: Honoraria (self): Chugai Pharma. S. Kuyama: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Chugai pharma; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Meiji. Y. Tsubata: Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony: Chugai Pharma; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Ono Pharmaceutical . T. Kato: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Advisory / Consultancy: Nitto Denko; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self): Roche; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Merck Sharp & Dohme; Honoraria (self): Novartis; Honoraria (self): Sumitomo Dainippon Pharma; Honoraria (self): Quintiles; Honoraria (self): Takeda; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (self): Kyorin; Research grant / Funding (self): Regeneron. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Honoraria (self), Advisory / Consultancy: Celltrion; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self): Kyowa Hakko Kirin; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Ignyta. K. Goto: Honoraria (self), Advisory / Consultancy: Otsuka; Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): AstraZeneca ; Honoraria (self), Research grant / Funding (self): Pfizer ; Honoraria (self), Research grant / Funding (self): Chugai Pharma; Honoraria (self), Research grant / Funding (self): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (self): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Eli Lilly; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self): Quintiles ; Honoraria (self), Research grant / Funding (self): Merck Serono; Honoraria (self), Research grant / Funding (self): Life Technologies; Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self): AbbVie ; Honoraria (self), Research grant / Funding (self): Riken Genesis ; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant / Funding (self): Takeda; Research grant / Funding (self): Sumitomo Dainippon Pharma ; Honoraria (self): SRL Diagnostics; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Kyowa Hakko Kirin; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): Eisai ; Research grant / Funding (self): Ignyta; Research grant / Funding (self): RTI Health Solutions; Research grant / Funding (self): Janssen; Research grant / Funding (self): Xcoo; Research grant / Funding (self): Loxo. All other authors have declared no conflicts of interest.

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