Summary
No report has assessed the differences in adverse event (AE) profiles of anticancer drugs for all types of cancers in clinical trials involving Japanese patients. This study aimed to compare the safety outcomes of anticancer drugs in Japanese and non-Japanese patients in multi-regional clinical trials (MRCTs), regardless of the type of cancer or drug. All new approvals of oncology drugs in Japan from January 2009 to December 2018 were searched through the Pharmaceuticals and Medical Devices Agency website. The odds ratio (OR) for comparing the incidence of AEs between Japanese and non-Japanese patients was estimated using the Mantel–Haenszel method with a random effect model. Sixty-six multi-regional phase 3 trials were identified involving 43,712 patients. Severe AE, AE leading to dose reduction, and AE leading to dose interruption were significantly more frequent in Japanese patients than in non-Japanese (odds ratios [ORs] were 1.32 (95% confidence interval (CI): 1.13–1.53), 1.97 (95% CI: 1.66–2.31), and 1.63 (95% CI: 1.43–1.86), respectively). Serious AEs (SAEs) and AEs leading to death were significantly less frequent in Japanese patients (OR: 0.70 (95% CI: 0.62–0.77) vs. 0.56 (95% CI: 0.44–0.67), respectively). There were no differences in AEs leading to study withdrawal. The incidence of most AEs was significantly higher in Japanese patients. In Japanese patients, the incidence of SAEs and AEs leading to death was low, but severe AEs, AEs leading to dose reductions, AEs leading to dose interruption, and individual adverse events were high.
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The datasets were generated and analyzed from published data source which were in References of this manuscript or PMDA website (https://www.pmda.go.jp/english/index.html).
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T.T. contributed to the data acquisition, statistical analysis and manuscript writing. T.T. and M.N. contributed to the conception of this research, interpretation of data, and reviewed and revised the manuscript critically for important intellectual content. T.T. and M.N. read and approved the final manuscript.
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This research study was conducted retrospectively from published data, and does not contain any studies with human participants or animals performed by any of the authors. No need for ethical approval by the Research Ethics Committee of Kitasato University in view of the retrospective nature of the study and informed consent.
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The manuscript does not contain individual patient data. Written informed consent for publication was obtained from all participants when all participants joined each clinical study.
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Toshiyuki Tamai is an employee of Eisai Co., Ltd.
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Tamai, T., Narukawa, M. Comparison of safety outcomes of anticancer drugs in Japanese and non-Japanese patients in multi-regional clinical trials: meta-analysis of safety profiles. Invest New Drugs 41, 483–492 (2023). https://doi.org/10.1007/s10637-023-01362-7
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DOI: https://doi.org/10.1007/s10637-023-01362-7