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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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.
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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.
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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