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Comparison of Standard Initial Dose and Reduced Initial Dose Regorafenib for Colorectal Cancer Patients: A Retrospective Cohort Study

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Abstract

Background

The benefit of regorafenib for colorectal cancer patients was demonstrated in previous randomized studies. However, these studies showed a high rate of treatment-related adverse events, and adverse events were more common in Japanese patients. Some studies showed fewer adverse events and a longer survival time with a reduced initial dose. However, the benefits of a reduced initial dose of regorafenib have only been evaluated in small samples.

Objective

Our objective was to analyze the efficacy of initial regorafenib dose reduction compared with a standard dose for colorectal cancer patients.

Patients and methods

We used a hospital-based nationwide claims database. Patients who received regorafenib for metastatic colorectal cancer between June 2013 and July 2017 were included in this study. We divided the patients into a standard initial dose group (standard group) and a reduced initial dose group (reduced group). Overall survival (OS) and adverse events were compared between the two groups. We performed propensity score matching for sensitivity analysis.

Results

We included 2376 patients (1208 in the standard group and 1168 in the reduced group). The median OS was 12.3 months (95% confidence interval (CI): 11.0–13.3) in the standard group and 12.6 months (95% CI: 11.7–13.6) in the reduced group. A log-rank test showed no significant difference between the two groups (p = 0.41). Most adverse events occurred less frequently in the reduced group. In the sensitivity analysis, there was no significant difference for OS.

Conclusions

No significant difference was observed for OS between the standard group and the reduced group. However, there were fewer adverse events in the reduced group. The optimal initial dose of regorafenib should be identified in further studies.

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Data Availability

The datasets generated and/or analyzed during the current study are not publicly available due to a contract with Medical Data Vision Co, Ltd. but are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Dr. Masato Takeuchi for advice on the revised manuscript.

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Authors and Affiliations

  1. Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida-konoecho, Sakyo-ku, Kyoto, 606-8501, Japan

    Masayuki Nakashima, Kazuki Ide & Koji Kawakami

  2. Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Yoshida-konoecho, Sakyo-ku, Kyoto, 606-8501, Japan

    Kazuki Ide & Koji Kawakami

Authors
  1. Masayuki Nakashima
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  2. Kazuki Ide
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Corresponding author

Correspondence to Koji Kawakami.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Koji Kawakami receives honoraria from Shin Nippon Biomedical Laboratories, LTD.; research funds from: Olympus Corporation, Sumitomo Dainippon Pharma Co., Ltd., Bayer Yakuhin Ltd., Stella Pharma Corporation, Novartis Pharma K.K., CMIC Co., Ltd., Amgen Astellas BioPharma K.K., Suntory Beverage & Food Ltd., Medical Platform Co., Ltd.; and holds stocks of: School Health Record Center Co., Ltd. and Real World Data, Co., Ltd. There are no patent products under development or marketed products to declare, relevant to those companies. Masayuki Nakashima and Kazuki Ide declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Nakashima, M., Ide, K. & Kawakami, K. Comparison of Standard Initial Dose and Reduced Initial Dose Regorafenib for Colorectal Cancer Patients: A Retrospective Cohort Study. Targ Oncol 14, 295–306 (2019). https://doi.org/10.1007/s11523-019-00642-8

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  • DOI: https://doi.org/10.1007/s11523-019-00642-8

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