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Gastrointestinal perforation following dabrafenib and trametinib administration in non-small cell lung carcinoma with BRAF V600E mutation: a case report and literature review

Summary

Gastrointestinal perforation related to mitogen-activated protein kinase kinase (MEK) inhibitors has been reported previously; however, there has been no case report of such a condition in patients with non-small cell lung cancer (NSCLC). Herein, we report a case of small intestinal perforation secondary to dabrafenib and trametinib administration, but not related to tumor regression. A 62-year-old man with non-small cell lung cancer harboring BRAF V600E mutation was treated with dabrafenib and trametinib. Four months after the initiation of treatment, a small intestinal perforation was diagnosed. Dabrafenib and trametinib rechallenge was performed after gastrointestinal perforation. The patient responded well to therapy and did not experience recurrence of gastrointestinal perforation. To the best of our knowledge, this is the first report of gastrointestinal perforation in a patient with NSCLC treated with a MEK inhibitor. The mechanism and risk factors of trametinib-induced perforation are currently unknown. Physicians should be aware of such severe gastrointestinal side effects of trametinib.

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Data availability

All related datas are presented in this paper, further inofrmation or datas are available on a reasonable request.

Abbreviations

BRAF:

V-raf murine sarcoma viral oncogene homolog B1

MEK:

Mitogen-activated protein kinase kinase

CT:

Computed tomography

NSCLC:

Non-small cell lung cancer

PR:

Partial response

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Acknowledgements

The authors would like to thank Keiko Sakuragawa and Kanako Masuta for their administrative assistance, and Motoko Mizumoto for operation of the case.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yuri Shimada, Yuki Sato, Ryo Tachikawa and Shigeo Hara. The first draft of the manuscript was written by Yuri Shimada and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yuki Sato.

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Ethical approval and consent to participate

All procedures performed in studies involving human participants 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.

Competing interests

Dr. Sato and Dr. Tomii have received lecture fees from Novartis Pharma K.K. (Tokyo, Japan). All remaining authors have no conflicts of interest to declare. We wish to confirm that there are no other known conflicts of interest associated with this publication. Further, there was no significant financial support for this work that could have influenced its outcome.

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Shimada, Y., Sato, Y., Tachikawa, R. et al. Gastrointestinal perforation following dabrafenib and trametinib administration in non-small cell lung carcinoma with BRAF V600E mutation: a case report and literature review. Invest New Drugs 39, 1702–1706 (2021). https://doi.org/10.1007/s10637-021-01135-0

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  • DOI: https://doi.org/10.1007/s10637-021-01135-0

Keywords

  • BRAF/MEK inhibitor
  • Gastrointestinal side effect
  • Small intestinal perforation
  • Lung cancer
  • Rechallenge