PMID- 37323187
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230918
IS  - 1758-8340 (Print)
IS  - 1758-8359 (Electronic)
IS  - 1758-8340 (Linking)
VI  - 15
DP  - 2023
TI  - Prospective exosome-focused translational research for afatinib (EXTRA) study of 
      patients with nonsmall cell lung cancer harboring EGFR mutation: an observational 
      clinical study.
PG  - 17588359231177021
LID - 10.1177/17588359231177021 [doi]
LID - 17588359231177021
AB  - BACKGROUND: The exosome-focused translational research for afatinib (EXTRA) study 
      is the first trial to identify novel predictive biomarkers for longer treatment 
      efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) 
      mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive 
      association study using genomic, proteomic, epigenomic, and metabolomic analyses. 
      OBJECTIVES: We report details of the clinical portion prior to omics analyses. 
      DESIGN: A prospective, single-arm, observational study was conducted using 
      afatinib 40 mg/day as an initial dose in untreated patients with EGFR 
      mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed. 
      METHODS: Progression-free survival (PFS), overall survival (OS), and adverse 
      events (AEs) were evaluated. RESULTS: A total of 103 patients (median age 
      70 years, range 42-88 years) were enrolled from 21 institutions in Japan between 
      February 2017 and March 2018. After a median follow-up of 35.0 months, 21% 
      remained on afatinib treatment, whereas 9% had discontinued treatment because of 
      AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median 
      afatinib treatment duration in patients with final doses of 40 (n = 27), 30 
      (n = 23), and 20 mg/day (n = 35), and 20 mg every other day (n = 18) were 13.4, 
      15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 
      3-year OS rate of 58.5%. The median OS in patients who did (n = 25) and did not 
      (n = 78) receive osimertinib during the entire course of treatment were 
      42.4 months and not reached, respectively (p = 0.654). CONCLUSIONS: As the 
      largest prospective study in Japan, this study confirmed favorable OS following 
      first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world 
      setting. Further analysis of the EXTRA study is expected to identify novel 
      predictive biomarkers for afatinib. TRIAL REGISTRATION: UMIN-CTR identifier 
      (UMIN000024935, 
      https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688.
CI  - (c) The Author(s), 2023.
FAU - Takata, Saori
AU  - Takata S
AD  - Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 
      Japan.
FAU - Morikawa, Kei
AU  - Morikawa K
AUID- ORCID: 0000-0002-0745-5118
AD  - Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna 
      University School of Medicine, Kanagawa, Japan.
FAU - Tanaka, Hisashi
AU  - Tanaka H
AD  - Department of Respiratory Medicine, Hirosaki University Graduate School of 
      Medicine, Aomori, Japan.
FAU - Itani, Hidetoshi
AU  - Itani H
AD  - Department of Respiratory Medicine, Ise Red Cross Hospital, Mie, Japan.
FAU - Ishihara, Masashi
AU  - Ishihara M
AD  - Division of Medical Oncology, Department of Internal Medicine, Teikyo University 
      School of Medicine, Tokyo, Japan.
FAU - Horiuchi, Kazuya
AU  - Horiuchi K
AD  - Respiratory Disease Center, Showa University Northern Yokohama Hospital, 
      Kanagawa, Japan.
FAU - Kato, Yasuhiro
AU  - Kato Y
AUID- ORCID: 0000-0001-8585-1995
AD  - Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan 
      Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
FAU - Ikemura, Shinnosuke
AU  - Ikemura S
AD  - Clinical and Translational Research Center, Keio University Hospital, Tokyo, 
      Japan.
FAU - Nakagawa, Hideyuki
AU  - Nakagawa H
AD  - Department of Respiratory Medicine, National Hospital Organization Hirosaki 
      Hospital, Aomori, Japan.
FAU - Nakahara, Yoshiro
AU  - Nakahara Y
AD  - Department of Respiratory Medicine, Kitasato University School of Medicine, 
      Kanagawa, Japan.
FAU - Seki, Yoshitaka
AU  - Seki Y
AD  - Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, 
      Japan.
FAU - Bessho, Akihiro
AU  - Bessho A
AUID- ORCID: 0000-0002-0394-7377
AD  - Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, 
      Japan.
FAU - Takahashi, Nobumasa
AU  - Takahashi N
AD  - Department of General Thoracic Surgery, Saitama Cardiovascular and Respiratory 
      Center, Saitama, Japan.
FAU - Hayashi, Kentaro
AU  - Hayashi K
AD  - Division of Respiratory Medicine, Department of Internal Medicine, Nihon 
      University School of Medicine, Tokyo, Japan.
FAU - Endo, Takeo
AU  - Endo T
AD  - Department of Respiratory Medicine, National Hospital Organization Mito Medical 
      Center, Ibaraki, Japan.
FAU - Takeyama, Kiyoshi
AU  - Takeyama K
AD  - Department of Respiratory Medicine, Tokyo Women's Medical University School of 
      Medicine, Tokyo, Japan.
FAU - Maekura, Toshiya
AU  - Maekura T
AD  - Department of Respiratory Medicine, Hoshigaoka Medical Center, Osaka, Japan.
FAU - Takigawa, Nagio
AU  - Takigawa N
AUID- ORCID: 0000-0002-3835-5128
AD  - Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, 
      Japan.
FAU - Kawase, Akikazu
AU  - Kawase A
AD  - First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, 
      Japan.
FAU - Endoh, Makoto
AU  - Endoh M
AD  - Department of Thoracic Surgery, Yamagata Prefectural Central Hospital, Yamagata, 
      Japan.
FAU - Nemoto, Kenji
AU  - Nemoto K
AD  - Department of Respiratory Medicine, National Hospital Organization, 
      Ibarakihigashi National Hospital, Ibaraki, Japan.
FAU - Kishi, Kazuma
AU  - Kishi K
AD  - Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, 
      Tokyo, Japan.
FAU - Soejima, Kenzo
AU  - Soejima K
AD  - Clinical and Translational Research Center, Keio University Hospital, Tokyo, 
      Japan.
FAU - Okuma, Yusuke
AU  - Okuma Y
AD  - Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan 
      Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
FAU - Yoshimura, Kenichi
AU  - Yoshimura K
AD  - Department of Biostatistics, Medical Center for Translational and Clinical 
      Research, Hiroshima University Hospital, Hiroshima, Japan.
FAU - Saigusa, Daisuke
AU  - Saigusa D
AD  - Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, 
      Teikyo University, Tokyo, Japan.
FAU - Kanai, Yae
AU  - Kanai Y
AD  - Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
FAU - Ueda, Koji
AU  - Ueda K
AD  - Project for Realization of Personalized Cancer Medicine, Cancer Precision 
      Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
FAU - Togashi, Akira
AU  - Togashi A
AD  - Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.
FAU - Matsutani, Noriyuki
AU  - Matsutani N
AD  - Department of Surgery, Teikyo University Hospital, Mizonokuchi, Kanagawa, Japan.
FAU - Seki, Nobuhiko
AU  - Seki N
AD  - Division of Medical Oncology, Department of Internal Medicine, Teikyo University 
      School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230605
PL  - England
TA  - Ther Adv Med Oncol
JT  - Therapeutic advances in medical oncology
JID - 101510808
PMC - PMC10262622
OTO - NOTNLM
OT  - EGFR-TKI
OT  - afatinib
OT  - biomarker
OT  - exosome
OT  - nonsmall-cell lung cancer
OT  - omics
COIS- Hisashi Tanaka: personal fees as honoraria from Ono Pharmaceutical, Bristol Myers 
      Squibb, AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, and Pfizer; 
      Yoshitaka Seki: personal fees as honoraria from AstraZeneca, Eli Lilly, MSD, Ono 
      Pharmaceutical, Novartis, Taiho Pharmaceutical, Chugai Pharmaceutical, Boehringer 
      Ingelheim, Shionogi, Sanofi, Kyowa Kirin, Kyorin Pharmaceutical, and GSK; Kazuma 
      Kishi: research funding and personal fees as honoraria from Boehringer Ingelheim; 
      Yusuke Okuma: research funding and personal fees as honoraria from AstraZeneca 
      and Chugai Pharmaceutical; research funding from AbbVie; and personal fees as 
      honoraria from Eisai, Eli Lilly, MSD, Novartis, Ono Pharmaceutical, Takeda 
      Pharmaceutical, and Taiho Pharmaceutical; Akira Togashi: employee of Boehringer 
      Ingelheim; Nobuhiko Seki: research funding and personal fees as honoraria from 
      Eli Lilly, Ono Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Chugai 
      Pharmaceutical, Takeda Pharmaceutical, Nippon Kayaku, Pfizer, and Daiichi Sankyo; 
      research funding from Eisai and Shionogi; and personal fees as honoraria from 
      AstraZeneca, MSD, Bristol Myers Squibb, Novartis, and Kyowa Kirin. No potential 
      conflicts of interest were disclosed by the other authors.
EDAT- 2023/06/16 06:42
MHDA- 2023/06/16 06:43
PMCR- 2023/06/05
CRDT- 2023/06/16 03:55
PHST- 2023/02/10 00:00 [received]
PHST- 2023/05/02 00:00 [accepted]
PHST- 2023/06/16 06:42 [pubmed]
PHST- 2023/06/16 06:43 [medline]
PHST- 2023/06/16 03:55 [entrez]
PHST- 2023/06/05 00:00 [pmc-release]
AID - 10.1177_17588359231177021 [pii]
AID - 10.1177/17588359231177021 [doi]
PST - epublish
SO  - Ther Adv Med Oncol. 2023 Jun 5;15:17588359231177021. doi: 
      10.1177/17588359231177021. eCollection 2023.