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CAPP-seq analysis of circulating tumor DNA from patients with EGFR T790M–positive lung cancer after osimertinib

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Abstract

Background

We here applied cancer personalized profiling by deep sequencing (CAPP-seq) to analysis of circulating tumor DNA (ctDNA) to identify resistance mechanisms in osimertinib-treated patients with EGFR T790M–positive non–small cell lung cancer (NSCLC).

Methods

The study included patients with EGFR activating mutation–positive advanced NSCLC who were positive for T790M in tumor tissue or plasma after previous treatment with an EGFR tyrosine kinase inhibitor, who received osimertinib at Kindai University Hospital between August 2014 and September 2017, and for whom plasma collected after progression on osimertinib was available. Clinical data were extracted from medical records. Patients with innate resistance to osimertinib were defined as those whose best response was progressive disease or stable disease for < 6 months, whereas patients with a complete or partial response or stable disease for > 6 months were considered as having acquired resistance.

Results

We performed CAPP-seq for 20 patients at progression on osimertinib. Distinct patterns of genomic alterations were apparent in patients with innate versus acquired resistance. Mutations in PIK3CA, KRAS, or BRAF and copy number gain for EGFR, ERBB2, or MET were more common in patients with innate resistance than in those with acquired resistance. In addition, one patient who underwent a repeat biopsy was found to harbor the C797S mutation of EGFR after disease progression during osimertinib rechallenge, with this mutation not having been detected at the time of initial progression on osimertinib.

Conclusions

CAPP-seq analysis of ctDNA was able to identify potentially targetable genetic alterations in patients with osimertinib resistance.

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Acknowledgements

We thank Tomoki Yamanaka of Roche Diagnostics as well as Haruka Sakamoto, Yume Shinkai, Michiko Kitano, and Mami Kitano of Kindai University for technical support.

Funding

This work was supported by Nippon Boehringer Ingelheim.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Ryoji Kato, Hidetoshi Hayashi, Shinichiro Suzuki, Koji Haratani, Takayuki Takahama, Junko Tanizaki, Yoshikane Nonagase, Kaoru Tanaka, Takeshi Yoshida, Masayuki Takeda, Kimio Yonesaka, Hiroyasu Kaneda & Kazuhiko Nakagawa

  2. Department of Genome Biology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Kazuko Sakai & Kazuto Nishio

  3. Department of Medical Oncology, Kindai University Nara Hospital, 1248-1 Otoda-cho, Ikoma, Nara, 630-0293, Japan

    Takayuki Takahama

  4. Department of Medical Oncology, Kishiwada City Hospital, 1001 Gakuhara-cho, Kishiwada-shi, Osaka, 596-8501, Japan

    Junko Tanizaki & Yoshikane Nonagase

  5. Department of Clinical Oncology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka City, Osaka, 545-8585, Japan

    Hiroyasu Kaneda

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  1. Ryoji Kato
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Correspondence to Hidetoshi Hayashi.

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Conflict of interest

R. Kato has received lecture fees from Bristol-Myers Squibb Co. Ltd.; and honoraria from Eli Lilly Japan K.K. H. Hayashi has received honoraria from AstraZeneca K.K., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Merck Biopharma Co. Ltd., and Taiho Pharmaceutical Co. Ltd.; and research funding from AbbVie Inc., AC MEDICAL Inc., Astellas Pharma Inc., AstraZeneca K.K., Bristol-Myers Squibb Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., EPS Associates Co. Ltd., GlaxoSmithKline K.K., Japan Clinical Research Operations Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Merck Biopharma Co. Ltd., MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., PAREXEL International Corp., Pfizer Japan Inc., PPD-SNBL K.K., Quintiles Transnational Japan K.K., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Yakult Honsha Co. Ltd. K. Sakai has received lecture fees from AstraZeneca K.K., Bio-Rad Laboratories, Inc., Chugai Pharmaceutical Co. Ltd., and Roche Diagnostics K.K., SRL, Inc. S. Suzuki has declared no conflicts of interest.K. Haratani has received honoraria from AstraZeneca K.K.; lecture fees from AS ONE Corporation, AstraZeneca K.K., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD K.K., and Pfizer Japan Inc.; and research funding from AstraZeneca K.K. T. Takahama has received honoraria from AstraZeneca K.K., Roche Diagnostics K.K., and Nippon Boehringer Ingelheim Co. Ltd. J. Tanizaki has received honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co. Ltd, Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., MSD K.K., and Taiho Pharmaceutical Co. Ltd. Y. Nonagase has received honoraria from Taiho Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co. Ltd. K. Tanaka has received honoraria from AstraZeneca KK, Bristol-Myers Squibb, Eisai Co. Ltd., Merck Biopharma Co., and Ono Pharmaceutical Co. Ltd. T. Yoshida has received lecture fees from Bristol-Myers Squibb Co. Ltd., Daiichi Sankyo Co. Ltd., Hisamitsu Pharmaceutical Co. Inc., MundiPharma K.K., and Shionogi & Co. Ltd. M. Takeda has received honoraria from Chugai Pharmaceutical Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., and Ono Pharmaceutical Co. Ltd. K. Yonesaka has received research funding from Daiichi Sankyo Co. Ltd.; and honoraria from Nippon Boehringer Ingelheim Co. Ltd. H. Kaneda has received lecture fees from AstraZeneca K.K., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Nippon Kayaku Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Pfizer Japan Inc., Taiho Pharmaceutical Co. Ltd.; and research funding from Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., and Ono Pharmaceutical Co. Ltd. K. Nishio has received honoraria from AstraZeneca K.K., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., Guardant Health Inc., Kobayashi Pharmaceutical Co. Ltd., Life Technologies Japan Ltd., MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Roche Diagnostics K.K., Sanofi K.K., Solasia Pharma K.K., SymBio Pharmaceuticals Ltd., Takeda Pharmaceutical Co. Ltd., and Yakult Honsha Co. Ltd.; and research funding from Astellas Pharma Inc., Eli Lilly Japan K.K., Ignyta Inc., Korea Otsuka Co. Ltd., Life Technologies Japan Ltd., and Nippon Boehringer Ingelheim Co. Ltd. K. Nakagawa has received honoraria from Astellas Pharma Inc., AstraZeneca K.K., AYUMI Pharmaceutical Co., Bristol-Myers Squibb Co. Ltd., CareNet Inc., Chugai Pharmaceutical Co. Ltd., Clinical Trial Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Hisamitsu Pharmaceutical Co. Inc., KYORIN Pharmaceutical Co. Ltd., Medical Review Co. Ltd., MEDICUS SHUPPAN Publishers Co. Ltd., MSD K.K., NANZANDO Co. Ltd., Nichi-Iko Pharmaceutical Co. Ltd., Nikkei Business Publications Inc., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Pfizer Japan Inc., Reno. Medical K.K., and SymBio Pharmaceuticals Ltd., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Thermo Fisher Scientific K.K., YODOSHA Co. Ltd, and YOMIURI TELECASTING Co.; and research funding from A2 Healthcare Corp., AbbVie Inc., Astellas Pharma Inc., Bayer Yakuhin Ltd., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., CMIC Shift Zero K.K., Covance Inc., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., EP-CRSU Co. Ltd., EPS Co., EPS international Co. Ltd., GlaxoSmithKline K.K., GRITSTONE ONCOLOGY Inc., ICON Japan K.K., inVentiv Health Japan, IQVIA Services JAPAN K.K., Kissei Pharmaceutical Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Linical Co. Ltd., Merch Serono Co. Ltd., MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., PAREXEL International Corp., Pfizer Japan Inc., Quintiles Inc., SymBio Pharmaceuticals Ltd., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Yakult Honsha Co. Ltd.; and consulting or advisory fees from Astellas Pharma Inc., Eli Lilly Japan K.K., Ono Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co. Ltd.

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Kato, R., Hayashi, H., Sakai, K. et al. CAPP-seq analysis of circulating tumor DNA from patients with EGFR T790M–positive lung cancer after osimertinib. Int J Clin Oncol 26, 1628–1639 (2021). https://doi.org/10.1007/s10147-021-01947-3

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