Detection of the T790M mutation of EGFR in plasma of advanced non-small cell lung cancer patients with acquired resistance to tyrosine kinase inhibitors (West Japan oncology group 8014LTR study)

Takayuki Takahama, Kazuko Sakai, Masayuki Takeda, Koichi Azuma, Toyoaki Hida, Masataka Hirabayashi, Tetsuya Oguri, Hiroshi Tanaka, Noriyuki Ebi, Toshiyuki Sawa, Akihiro Bessho, Motoko Tachihara, Hiroaki Akamatsu, Shuji Bandoh, Daisuke Himeji, Tatsuo Ohira, Mototsugu Shimokawa, Yoichi Nakanishi, Kazuhiko Nakagawa, Kazuto Nishio

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Abstract

Introduction: Next-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been developed to overcome resistance to earlier generations of such drugs mediated by a secondary T790M mutation of EGFR, but the performance of a second tumor biopsy to assess T790M mutation status can be problematic. Methods: We developed and evaluated liquid biopsy assays for detection of TKIsensitizing and T790M mutations of EGFR by droplet digital PCR (ddPCR) in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients with acquired EGFRTKI resistance. Results: A total of 260 patients was enrolled between November 2014 and March 2015 at 29 centers for this West Japan Oncology Group (WJOG 8014LTR) study. Plasma specimens from all subjects as well as tumor tissue or malignant pleural effusion or ascites fluid from 41 patients were collected after the development of EGFR-TKI resistance. All plasma samples were genotyped successfully and the results were reported to physicians within 14 days. TKI-sensitizing and T790M mutations were detected in plasma of 120 (46.2%) and 75 (28.8%) patients, respectively. T790M was detected in 56.7% of patients with plasma positive for TKI-sensitizing mutations. For the 41 patients with paired samples obtained after acquisition of EGFRTKI resistance, the concordance for mutation detection by ddPCR in plasma compared with tumor tissue or malignant fluid specimens was 78.0% for TKI-sensitizing mutations and 65.9% for T790M. Conclusions: Noninvasive genotyping by ddPCR with cell-free DNA extracted from plasma is a promising approach to the detection of gene mutations during targeted treatment.

Original languageEnglish
Pages (from-to)58492-58499
Number of pages8
JournalOncotarget
Volume7
Issue number36
DOIs
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • Oncology

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    Takahama, T., Sakai, K., Takeda, M., Azuma, K., Hida, T., Hirabayashi, M., Oguri, T., Tanaka, H., Ebi, N., Sawa, T., Bessho, A., Tachihara, M., Akamatsu, H., Bandoh, S., Himeji, D., Ohira, T., Shimokawa, M., Nakanishi, Y., Nakagawa, K., & Nishio, K. (2016). Detection of the T790M mutation of EGFR in plasma of advanced non-small cell lung cancer patients with acquired resistance to tyrosine kinase inhibitors (West Japan oncology group 8014LTR study). Oncotarget, 7(36), 58492-58499. https://doi.org/10.18632/oncotarget.11303