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Meta-Analysis of Regorafenib-Associated Adverse Events and Their Management in Colorectal and Gastrointestinal Stromal Cancers

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Abstract

Introduction

To assess the risk factors associated with regorafenib-related adverse events (AEs) in metastatic colorectal cancer (mCRC) and gastrointestinal stromal tumors (GIST). We also evaluated different measures of combatting AEs and their success rate to aid physicians in early identification and management of reported AEs.

Methods

A literature search was conducted through the electronic databases PubMed, Embase, and Cochrane Central Register of Controlled Trials up to May 2018 according to the pre-specified inclusion and exclusion criteria. Pooled estimates with Pearson correlation were obtained with fixed or random-effects models.

Results

From our analysis, it was evident that AEs were more common in patients aged less than 65 years compared to those aged at least 65 years (71.3% vs. 27.6%, p = 0.001). A statistically significant correlation was observed between the occurrence of AEs and a dose of 160 mg (r = 0.967; p = 0.001) while no significant correlation was found at 120 mg and 80 mg. The common measures used to manage AEs included lowering the regorafenib dose (41%), intermittent drug withdrawal (66.7%), and complete drug withdrawal (19%). About 57% of patients recovered from AE after their initiating dose was lowered.

Conclusion

Regorafenib-associated AEs are more common at an initiating dose of 160 mg. Considering that the efficacy depends on the dosage, 120 mg might be a better choice for mCRC and GIST patients; further studies are needed to validate the results of our analysis. Further prompt identification and management of AEs are required to help the patients continue with drug therapy.

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Acknowledgements

All the investigators involved in the study contributed equally and has approved the final manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. No funding or sponsorship was received for this study or publication of this article. The article processing charges were funded by the authors.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

The authors of the paper (Ganfeng Xie, Yuzhu Gong, Shuang Wu, Chong Li, Songtao Yu, Zhe Wang, Jianfang Chen, Quanfeng Zhao, Jianjun Li, Houjie Liang) have nothing to disclose.

Compliance with Ethics Guidelines

This meta-analysis (CRD42018099548) was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines [16]. It is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. As such, the study was exempt from requiring IRB approval.

Data Availability

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

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Authors and Affiliations

  1. Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China

    Ganfeng Xie, Yuzhu Gong, Shuang Wu, Chong Li, Songtao Yu, Zhe Wang, Jianfang Chen, Jianjun Li & Houjie Liang

  2. Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China

    Quanfeng Zhao

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  1. Ganfeng Xie
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  2. Yuzhu Gong
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Correspondence to Houjie Liang.

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Xie, G., Gong, Y., Wu, S. et al. Meta-Analysis of Regorafenib-Associated Adverse Events and Their Management in Colorectal and Gastrointestinal Stromal Cancers. Adv Ther 36, 1986–1998 (2019). https://doi.org/10.1007/s12325-019-01013-5

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