Therapeutic Advances in Medical Oncology (Jun 2023)

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

  • Saori Takata,
  • Kei Morikawa,
  • Hisashi Tanaka,
  • Hidetoshi Itani,
  • Masashi Ishihara,
  • Kazuya Horiuchi,
  • Yasuhiro Kato,
  • Shinnosuke Ikemura,
  • Hideyuki Nakagawa,
  • Yoshiro Nakahara,
  • Yoshitaka Seki,
  • Akihiro Bessho,
  • Nobumasa Takahashi,
  • Kentaro Hayashi,
  • Takeo Endo,
  • Kiyoshi Takeyama,
  • Toshiya Maekura,
  • Nagio Takigawa,
  • Akikazu Kawase,
  • Makoto Endoh,
  • Kenji Nemoto,
  • Kazuma Kishi,
  • Kenzo Soejima,
  • Yusuke Okuma,
  • Kenichi Yoshimura,
  • Daisuke Saigusa,
  • Yae Kanai,
  • Koji Ueda,
  • Akira Togashi,
  • Noriyuki Matsutani,
  • Nobuhiko Seki

DOI
https://doi.org/10.1177/17588359231177021
Journal volume & issue
Vol. 15

Abstract

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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