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

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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.

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Acknowledgements

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

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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
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  2. Haruyasu Murakami
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  3. Haruki Kobayashi
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  4. Kazuhisa Nakashima
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  5. Shota Omori
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  6. Kazushige Wakuda
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  7. Akira Ono
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  8. Hirotsugu Kenmotsu
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  9. Tateaki Naito
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  10. Masahiro Endo
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  11. Toshiaki Takahashi
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Corresponding author

Correspondence to Takahisa Kawamura.

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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.

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Informed consent was obtained from the patient.

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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

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

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