Cancer Chemotherapy and Pharmacology

, Volume 83, Issue 5, pp 817–825 | Cite as

Re-challenge of afatinib after 1st generation EGFR-TKI failure in patients with previously treated non-small cell lung cancer harboring EGFR mutation

  • Ou Yamaguchi
  • Kyoichi KairaEmail author
  • Atsuto Mouri
  • Ayako Shiono
  • Kosuke Hashimoto
  • Yu Miura
  • Fuyumi Nishihara
  • Yoshitake Murayama
  • Kunihiko Kobayashi
  • Hiroshi Kagamu
Original Article



Re-challenge of erlotinib after gefitinib failure is reported to yield some benefit in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation. However, little is known about the re-challenge of afatinib after 1st generate on EGFR tyrosine kinase inhibitor (TKI) failure.


From May 2015 to August 2018, 62 patients with advanced NSCLC harboring sensitive EGFR mutation received afatinib after gefitinib and/or erlotinib failure at our institution was included in our retrospective study.


The overall response rate (ORR) and disease control rate (DCR) of afatinib as re-challenge were 17.0% and 79.2%, respectively. The median time on treatment of 1st generation EGFR-TKI (1st TKI) was 14 months. By multivariate analysis, smoking, performance status (PS), and time on treatment of 1st TKI with more than 10 months were confirmed to be independent prognostic factors predicting a worse progression-free survival (PFS), and significant prognostic markers for overall survival (OS) were PS and time on treatment of 1st TKI with more than 10 months, especially in patients with exon 19 deletion.


Re-challenge of afatinib was identified as one of the therapeutic options after 1st TKI failure in the patients with advanced NSCLC harboring EGFR mutation when the time of treatment by prior 1st TKI is more than 10 months.


Afatinib Re-challenge EGFR mutation EGFR-TKI 



This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

OY, AM, KK, and HK have received research grants and a speaker honorarium from Boehringer Ingelheim Company. All remaining authors have declared no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ou Yamaguchi
    • 1
  • Kyoichi Kaira
    • 1
    Email author
  • Atsuto Mouri
    • 1
  • Ayako Shiono
    • 1
  • Kosuke Hashimoto
    • 1
  • Yu Miura
    • 1
  • Fuyumi Nishihara
    • 1
  • Yoshitake Murayama
    • 1
  • Kunihiko Kobayashi
    • 1
  • Hiroshi Kagamu
    • 1
  1. 1.Department of Respiratory Medicine Comprehensive Cancer Center, International Medical CenterSaitama Medical UniversityHidaka-CityJapan

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