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Cancer Chemotherapy and Pharmacology

, Volume 76, Issue 4, pp 835–841 | Cite as

EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer

  • Kyoko Otsuka
  • Akito Hata
  • Jumpei Takeshita
  • Chiyuki Okuda
  • Reiko Kaji
  • Katsuhiro Masago
  • Shiro Fujita
  • Nobuyuki Katakami
Original Article

Abstract

Background

Efficacies of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) rechallenge have been demonstrated in EGFR-mutant non-small cell lung cancer (NSCLC). However, their efficacies were only moderate. Some preclinical studies suggested synergistic effects of bevacizumab to EGFR-TKI in TKI-resistant models.

Methods

We retrospectively evaluated clinical efficacy and safety of EGFR-TKI rechallenge with bevacizumab. Rebiopsy was performed on all studied cases to examine T790M-resistant mutation status.

Results

Between January 2010 and June 2014, a total of 24 EGFR-mutant NSCLC patients who had been previously treated with EGFR-TKIs (gefitinib, erlotinib, and/or afatinib) received EGFR-TKI rechallenge with bevacizumab. Twenty-two (92 %) patients underwent erlotinib and two (8 %) gefitinib as rechallenge EGFR-TKIs in combination with bevacizumab. Three patients achieved partial response, and 18 had stable disease, resulting in the response rate (RR) of 13 % and disease control rate (DCR) of 88 %, respectively. The median progression-free survival (PFS) was 4.1 [95 % confidence interval (CI) 2.3–4.9] months, and the median overall survival (OS) was 13.5 (95 % CI 9.7–27.4) months. The RR, DCR, median PFS, and median OS for T790M-positive versus T790M-negative were 0 versus 18 % (p = 0.530), 86 versus 88 % (p = 1.00), 3.3 versus 4.1 months (p = 0.048), and 15.1 versus 13.5 months (p = 0.996), respectively. Severe adverse events (≥grade 3): grade 3 of 1 (4 %) rash; grade 3 of 1 (4 %) paronychia; grade 3 of 1 (4 %) hypertension; and grade 3 of 1 (4 %) anemia, were observed.

Conclusions

EGFR-TKI rechallenge with bevacizumab demonstrated higher DCR and modestly longer PFS than historical data on EGFR-TKI rechallenge alone. Its activity was notably higher in T790M-negative population.

Keywords

EGFR mutation EGFR-TKI rechallenge Bevacizumab Acquired resistance T790M 

Notes

Acknowledgments

We thank Mr. David Martin for writing support.

Compliance with ethical standards

Conflict of interest

No conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Kyoko Otsuka
    • 1
  • Akito Hata
    • 1
  • Jumpei Takeshita
    • 1
  • Chiyuki Okuda
    • 1
  • Reiko Kaji
    • 1
  • Katsuhiro Masago
    • 1
  • Shiro Fujita
    • 1
  • Nobuyuki Katakami
    • 1
  1. 1.Division of Integrated OncologyInstitute of Biomedical Research and InnovationKobeJapan

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