Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring <i>EGFR</i> mutation: an observational clinical study-Reference-Cited by-同舟云学术

Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study

Published:2023-01 Issue: Volume:15 Page:175883592311770
ISSN:1758-8359
Container-title:Therapeutic Advances in Medical Oncology
language:en
Short-container-title:Ther Adv Med Oncol

Author:

Takata Saori¹,Morikawa Kei²^ORCID,Tanaka Hisashi³,Itani Hidetoshi⁴,Ishihara Masashi⁵,Horiuchi Kazuya⁶,Kato Yasuhiro⁷^ORCID,Ikemura Shinnosuke⁸,Nakagawa Hideyuki⁹,Nakahara Yoshiro¹⁰,Seki Yoshitaka¹¹,Bessho Akihiro¹²^ORCID,Takahashi Nobumasa¹³,Hayashi Kentaro¹⁴,Endo Takeo¹⁵,Takeyama Kiyoshi¹⁶,Maekura Toshiya¹⁷,Takigawa Nagio¹⁸^ORCID,Kawase Akikazu¹⁹,Endoh Makoto²⁰,Nemoto Kenji²¹,Kishi Kazuma²²,Soejima Kenzo⁸,Okuma Yusuke⁷,Yoshimura Kenichi²³,Saigusa Daisuke²⁴,Kanai Yae²⁵,Ueda Koji²⁶,Togashi Akira²⁷,Matsutani Noriyuki²⁸,Seki Nobuhiko²⁹

Affiliation:

1. Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan

2. Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan

3. Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Aomori, Japan

4. Department of Respiratory Medicine, Ise Red Cross Hospital, Mie, Japan

5. Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan

6. Respiratory Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan

7. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

8. Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan

9. Department of Respiratory Medicine, National Hospital Organization Hirosaki Hospital, Aomori, Japan

10. Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan

11. Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan

12. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan

13. Department of General Thoracic Surgery, Saitama Cardiovascular and Respiratory Center, Saitama, Japan

14. Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

15. Department of Respiratory Medicine, National Hospital Organization Mito Medical Center, Ibaraki, Japan

16. Department of Respiratory Medicine, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan

17. Department of Respiratory Medicine, Hoshigaoka Medical Center, Osaka, Japan

18. Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan

19. First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan

20. Department of Thoracic Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan

21. Department of Respiratory Medicine, National Hospital Organization, Ibarakihigashi National Hospital, Ibaraki, Japan

22. Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Tokyo, Japan

23. Department of Biostatistics, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan

24. Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan

25. Department of Pathology, Keio University School of Medicine, Tokyo, Japan

26. Project for Realization of Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan

27. Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan

28. Department of Surgery, Teikyo University Hospital, Mizonokuchi, Kanagawa, Japan

29. Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan

Abstract

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

Funder

Boehringer Ingelheim

Publisher

SAGE Publications

Subject

Oncology

Link

http://journals.sagepub.com/doi/pdf/10.1177/17588359231177021

Reference36 articles.

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