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Evaluation of lung adverse events with trastuzumab using the Japanese pharmacovigilance database

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Abstract

The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 4362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary edema, pleural effusion, lung disorder, acute pulmonary edema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105 days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful to Professor Yoshihiro Uesawa from the Department of Medical Molecular Informatics, Meiji Pharmaceutical University. We are also grateful to Tadashi Hirooka (TAIHO PHARMA Corporation) for his lecture on Hirooka methods using the JADER database.

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The authors have not disclosed any funding.

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Authors and Affiliations

  1. Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan

    Yuko Kanbayashi

  2. Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences, Doshisha Women’s College of Liberal Arts, 97-1, Kodominamihokotate, Kyotanabe-shi, Kyoto, Japan

    Mayako Uchida, Misui Kashiwagi & Hitomi Akiba

  3. School of Pharmacy, Hyogo Medical University, 1-3-6 Minatojima, Kobe, Hyogo, Japan

    Tadashi Shimizu

Authors
  1. Yuko Kanbayashi
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  4. Hitomi Akiba
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  5. Tadashi Shimizu
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Contributions

YK and MU contributed to data curation; writing of the original draft; and writing, reviewing, and editing of the manuscript. MK and HA contributed to data curation and writing, reviewing, and editing of the manuscript. TS contributed to conceptualisation; supervision; and writing, reviewing, and editing of the manuscript.

Corresponding author

Correspondence to Yuko Kanbayashi.

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All authors declare no conflict of interest.

Ethical approval

Ethics approval was not sought for this study; given the database-related, observational design without direct involvement of any research subjects. All results were obtained from data openly available online from the PMDA website (www.pmda.go.jp). All data from the JADER database were fully anonymized by the relevant regulatory authority before we accessed them. Thus, all methods were performed in accordance with the relevant guidelines and regulations.

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Kanbayashi, Y., Uchida, M., Kashiwagi, M. et al. Evaluation of lung adverse events with trastuzumab using the Japanese pharmacovigilance database. Med Oncol 39, 219 (2022). https://doi.org/10.1007/s12032-022-01805-w

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