Skip to main content

Advertisement

SpringerLink
Log in

Leptomeningeal recurrence after long-term alectinib therapy for non-small cell lung cancer harboring an EML4-ALK fusion protein

  • SHORT REPORT
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

The recent approval of anaplastic lymphoma kinase (ALK) inhibitors for the treatment of ALK-rearranged non-small cell lung cancer (NSCLC) has dramatically transformed cancer therapy. However, leptomeningeal metastases (LM) are frequent and often devastating complications of ALK-rearranged NSCLC, and treatment against LM remains challenging. Herein we report a case of a 19-year-old male diagnosed with ALK-rearranged NSCLC with LM. He experienced heavy treatment before introduction of alectinib therapy, which continued for approximately 5.5 years with marked efficacy. However, he experienced recurrence of a bulbar metastasis after discontinuation of alectinib. Reintroduction of standard-dose alectinib therapy resolved the lesion again. Our findings suggest that ALK-tyrosine kinase inhibitor therapy should be continued in patients showing a long-term complete response, unless intolerable toxicities are present, and that rechallenge treatment with alectinib may represent a therapeutic option for central nervous system metastases.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T (2017) Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet 390:29–39

    Article  CAS  Google Scholar 

  2. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Pérol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T, ALEX Trial Investigators (2017) Alectinib versus Crizotinib in untreated ALK-positive non-small-cell lung Cancer. N Engl J Med 377:829–838

    Article  CAS  PubMed  Google Scholar 

  3. Kodama T, Hasegawa M, Takanashi K, Sakurai Y, Kondoh O, Sakamoto H (2014) Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases. Cancer Chemother Pharmacol 74:1023–1028

    Article  CAS  PubMed  Google Scholar 

  4. Gainor JF, Ou SH, Logan J et al (2013) The central nervous system as a sanctuary site in ALK-positive non-small-cell lung cancer. J Thorac Oncol 8:1570–1573

    Article  CAS  PubMed  Google Scholar 

  5. Gainor JF, Chi AS, Logan J, Hu R, Oh KS, Brastianos PK, Shih HA, Shaw AT (2016) Alectinib dose escalation Reinduces central nervous system responses in patients with anaplastic lymphoma kinase-positive non-small cell lung Cancer relapsing on standard dose Alectinib. J Thorac Oncol 11:256–260

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Clare Cox, PhD, and Alison Sherwin, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Takahisa Kawamura, Haruyasu Murakami, Haruki Kobayashi, Kazuhisa Nakashima, Shota Omori, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito & Toshiaki Takahashi

  2. Division of Diagnostic Radiology, Shizuoka Cancer Center Hospital, Shizuoka, Japan

    Masahiro Endo

Authors
  1. Takahisa Kawamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haruyasu Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haruki Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazuhisa Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shota Omori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazushige Wakuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akira Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hirotsugu Kenmotsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tateaki Naito
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Masahiro Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Toshiaki Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takahisa Kawamura.

Ethics declarations

Conflict of interest

Haruyasu Murakami has received honoraria from Boehringer Ingelheim, Pfizer, Chugai Pharma, Taiho Pharmaceutical, AstraZeneca, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Novartis, Merck Sharp & Dohme, and a grant from AstraZeneca. Haruki Kobayashi has received honoraria from MSD K.K. and Taiho Pharmaceutical. Kazuhisa Nakashima has received honoraria from Chugai Pharma, Boeringer Ingelheim and Novartis Pharma. Shota Omori has received honoraria from MSD K.K. Kazushige Wakuda has received honoraria from AstraZeneca, Chugai Pharmaceutical, Boeringer Ingelheim, Eli Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, and a grant from AstraZeneca. Akira Ono has received honoraria from Chugai Pharmaceutical, Taiho Pharmaceutical, Ono Pharmaceutical, and grants from Chugai Pharma and Taiho Pharmaceutical. Hirotsugu Kenmotsu has received honoraria from AstraZeneca, Chugai Pharmaceutical, Bristol-Myers, Boeringer Ingelheim, Eli Lilly, Kyowa Hakko Kirin, MSD K.K., Novartis Pharma, and grants from AstraZeneca, Chugai Pharmaceutical and Boehringer Ingelheim. Tateaki Naito has received honoraria from Ono Pharmaceutical. Masahiro Endo has received honoraria from AstraZeneca and Ono Pharmaceutical. Toshiaki Takahashi has received honoraria from Eli Lilly, AstraZeneca, Chugai Pharma, MSD, Ono Pharmaceutical, Novartis Pharma, Roche Diagnostics, and grants from Eli Lilly, AstraZeneca, Chugai Pharma, MSD, and Ono Pharmaceutical. For the remaining authors no conflicts of interest are declared.

Ethical approval

All procedures performed on the patient were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from the patient.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kawamura, T., Murakami, H., Kobayashi, H. et al. Leptomeningeal recurrence after long-term alectinib therapy for non-small cell lung cancer harboring an EML4-ALK fusion protein. Invest New Drugs 37, 184–187 (2019). https://doi.org/10.1007/s10637-018-0633-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-018-0633-6

Keywords

Search

Navigation