Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

A Correction to this article was published on 08 November 2019

This article has been updated

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Change history

  • 08 November 2019

    In the original publication of the article, the authors found few errors and the corrections are given below:

  • 08 November 2019

    In the original publication of the article, the authors found few errors and the corrections are given below:

References

  1. Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388

    Article  CAS  Google Scholar 

  2. Sequist LV, Yang JC, Yamamoto N et al (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31:3327–3334

    Article  CAS  Google Scholar 

  3. Soria JC, Ohe Y, Vansteenkiste J et al (2018) Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 378:113–125

    Article  CAS  Google Scholar 

  4. Park K, Tan EH, O’Byrne K et al (2016) Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol 17:577–589

    Article  CAS  Google Scholar 

  5. Wu YL, Cheng Y, Zhou X et al (2017) Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol 18:1454–1466

    Article  CAS  Google Scholar 

  6. Asahina H, Oizumi S, Inoue A et al (2010) Phase II study of gefitinib re-administration in patients with advanced non-small cell lung cancer and previous response to gefitinib. Oncology 79:423–429

    Article  CAS  Google Scholar 

  7. Koizumi T, Agatsuma T, Ikegami K et al (2012) Prospective study of gefitinib readministration after chemotherapy in patients with advanced non-small-cell lung cancer who previously responded to gefitinib. Clin Lung Cancer 13:458–463

    Article  CAS  Google Scholar 

  8. Oh IJ, Ban HJ, Kim KS et al (2012) Retreatment of gefitinib in patients with non-small cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study. Lung Cancer 77:121–127

    Article  Google Scholar 

  9. Miller VA, Hirsh V, Cadranel J et al (2012) Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 13:528–538

    Article  CAS  Google Scholar 

  10. Katakami N, Atagi S, Goto K et al (2013) LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol 31:3335–3341

    Article  CAS  Google Scholar 

  11. Tomizawa Y, Fujita Y, Tamura A et al (2010) Effect of gefitinib re-challenge to initial gefitinib responder with nonsmall cell lung cancer followed by chemotherapy. Lung Cancer 68:269–272

    Article  Google Scholar 

  12. Kaira K, Naito T, Takahashi T et al (2010) Pooled analysis of the reports of erlotinib after failure of gefitinib for non-small cell lung cancer. Lung Cancer 68:99–104

    Article  Google Scholar 

  13. Oda N, Hotta K, Ninomiya K et al (2018) A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation: Okayama Lung Cancer Study Group trial 1403. Cancer Chemother Pharmacol 82:1031–1038

    Article  CAS  Google Scholar 

  14. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumour: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  CAS  Google Scholar 

  15. Hochmair MJ, Morabito A, Hao D et al (2018) Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: an observational study. Future Oncol 14:2861–2874

    Article  CAS  Google Scholar 

  16. Cho KM, Keam B, Kim TM et al (2015) Clinical efficacy of erlotinib, a salvage treatment for non-small cell lung cancer patients following gefitinib failure. Korean J Intern Med 30:891–898

    Article  CAS  Google Scholar 

  17. Cho BC, Im CK, Park MS et al (2007) Phase II study of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib. J Clin Oncol 25:2528–2533

    Article  CAS  Google Scholar 

  18. Wong AS, Soong R, Seah SB et al (2008) Evidence for disease control with erlotinib after gefitinib failure in typical gefitinib-sensitive Asian patients with non-small cell lung cancer. J Thorac Oncol 3:400–404

    Article  Google Scholar 

  19. Choong NW, Dietrich S, Seiwert TY et al (2006) Gefitinib response of erlotinib-refractory lung cancer involving meninges–role of EGFR mutation. Nat Clin Pract Oncol 3:50–57

    Article  CAS  Google Scholar 

  20. Zhang Z, Lee JC, Lin L et al (2012) Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet 44:852–860

    Article  CAS  Google Scholar 

  21. Yang JC, Wu YL, Schuler M et al (2015) Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 16:141–151

    Article  CAS  Google Scholar 

  22. Yang JC, Sequist LV, Zhou C et al (2016) Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol 27:2103–2110

    Article  Google Scholar 

Download references

Funding

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

Author information

Authors and Affiliations

  1. Department of Respiratory Medicine Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan

    Ou Yamaguchi, Kyoichi Kaira, Atsuto Mouri, Ayako Shiono, Kosuke Hashimoto, Yu Miura, Fuyumi Nishihara, Yoshitake Murayama, Kunihiko Kobayashi & Hiroshi Kagamu

Authors
  1. Ou Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoichi Kaira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atsuto Mouri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayako Shiono
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kosuke Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fuyumi Nishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshitake Murayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kunihiko Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hiroshi Kagamu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyoichi Kaira.

Ethics declarations

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.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamaguchi, O., Kaira, K., Mouri, A. et al. Re-challenge of afatinib after 1st generation EGFR-TKI failure in patients with previously treated non-small cell lung cancer harboring EGFR mutation. Cancer Chemother Pharmacol 83, 817–825 (2019). https://doi.org/10.1007/s00280-019-03790-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-019-03790-w

Keywords

Search

Navigation