@article{c886fcc297a14a54b8336a3afe30b31b,
title = "Prospective exosome-focused translational research for afatinib study of non-small cell lung cancer patients expressing EGFR (EXTRA study)",
abstract = "Patients with EGFR-mutated non-small cell lung cancer (NSCLC) exhibit resistance to EGFR-tyrosine kinase inhibitors (TKIs) within 9–14 months of therapy. Recently, EGFR-mutated NSCLC has demonstrated the potential for heterogeneity; therefore, the manner of clonal heterogeneity may impact the duration of progression-free and overall survival and other parameters affecting EGFR-TKI treatment efficacy. However no predictive biomarker of these favorable treatment efficacies has been identified to date. The exosome-focused translational research for afatinib (EXTRA) study aims to identify a novel predictive biomarker and a resistance marker for afatinib by analyzing data from association studies of the clinical efficacy of afatinib and four “OMICs” (genomics, proteomics, epigenomics, and metabolomics) using peripheral blood from patients treated with afatinib. This study aims to: (i) conduct comprehensive multi-OMIC analyses in a prospective clinical trial, and (ii) focus on both sera/plasma and exosome as a source for OMIC analyses to identify a novel predictor of the efficacy of a specific drug. To eliminate the carryover bias of prior treatment, systemic treatment-na{\"i}ve patients were enrolled. The candidates to be screened for biomarkers comprise a discovery cohort of 60 patients and an independent validation cohort of 40 patients. The EXTRA study is the first trial to screen novel biomarkers of longer treatment efficacy of EGFR-TKIs using four-OMICs analyses, focusing on both “naked or free” molecules and “capsulated” exosomal components in serially collected peripheral blood.",
keywords = "Afatinib, OMIC, epidermal growth factor receptor, exosome, translational research",
author = "Yusuke Okuma and Kei Morikawa and Hisashi Tanaka and Takuma Yokoyama and Hidetoshi Itani and Kazuya Horiuchi and Hideyuki Nakagawa and Nobumasa Takahashi and Akihiro Bessho and Kenzo Soejima and Kazuma Kishi and Akira Togashi and Yae Kanai and Koji Ueda and Katsuhisa Horimoto and Noriyuki Matsutani and Nobuhiko Seki",
note = "Funding Information: YO received personal fees as honoraria from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical, and Ono Pharmaceutical. HT received personal fees as honoraria from Nippon Boehringer Ingelheim Co., Ltd. HN received research funding from AstraZeneca K.K., Pfizer Japan Inc., and Bristol–Myers Squibb Japan. AB received personal fees as honoraria from AstraZeneca K.K., Pfizer Japan Inc. KS received personal fees as honoraria from AstraZeneca K.K. and Chugai Pharmaceutical and received research funding from Chugai Pharmaceutical, Ono Pharmaceutical, and Taiho Pharmaceutical. KK received personal fees as honoraria from Nippon Boehringer Ingelheim Co., Ltd. AT is an employee of Nippon Boehringer Ingelheim Co., Ltd. and a visiting researcher of National Institute of Advanced Industrial Science and Technology (AIST). NS received personal fees as honoraria from Lily Japan, AstraZeneca K.K., Daiichi Sankyo, MSD Oncology, Chugai Pharmaceutical, and Ono Pharmaceutical, Nippon Boehringer Ingelheim Co., Ltd., and Bristol-Myers Squibb Japan and research funding from Nippon Boehringer Ingelheim Co., Ltd. Publisher Copyright: {\textcopyright} 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd",
year = "2019",
month = feb,
doi = "10.1111/1759-7714.12923",
language = "English",
volume = "10",
pages = "395--400",
journal = "Thoracic Cancer",
issn = "1759-7706",
publisher = "Blackwell Publishing Asia Pty Ltd",
number = "2",
}