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Regorafenib, TAS-102, or fruquintinib for metastatic colorectal cancer: any difference in randomized trials?

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Abstract

Purpose

Direct randomized comparisons of regorafenib, TAS-102, and fruquintinib for treating metastatic colorectal cancer (mCRC) are lacking. Here, we evaluated the efficacy and safety of three agents by a systematic review and a network meta-analysis.

Methods

We included phase III randomized controlled trials in the PubMed, Embase, and Scopus Cochrane databases and ClinicalTrials.gov registry from initiation until January 2019. Data from randomized controlled trials including overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were extracted. Direct meta-analysis and indirect meta-analysis using network meta-analysis were assessed.

Results

Five trials comprising a total of 2586 patients were included. For efficacy analysis of OS, no statistically significant differences were observed between regorafenib and TAS-102 (HR 0.945, 95% CI [0.677, 1.320], P = 0.753), regorafenib and fruquintinib (HR 1.056, 95% CI [0.690, 1.621], P = 0.814), or TAS-102 and fruquintinib (HR 1.117, 95% CI [0.740, 1.685], P = 0.610). However, fruquintinib was superior in PFS compared with TAS-102 (HR 1.756, 95% CI [1.079, 2.857], P = 0.023). Regorafenib and TAS-102 appeared to have a similar effect on PFS (HR 0.907, 95% CI [0.611, 1.346], P = 0.641), as did regorafenib and fruquintinib (HR 1.592, 95% CI [0.968, 2.618], P = 0.067). None of the three agents were better in terms of all grade AEs or any grade of 3–5 AEs. However, subgroup analysis of AEs exhibited different toxicity profiles between the three drugs.

Conclusions

Indirect comparison suggested that the three agents had similar OS but that fruquintinib was superior in terms of PFS compared with that of TAS-102. These three agents had different toxicity profiles.

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Acknowledgments

We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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  1. Qi Zhang and Qianqian Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Bei**g), Peking University Cancer Hospital and Institute, Bei**g, 100142, China

    Qi Zhang, **cheng Wang, Jian Li, Lin Shen & Zhi Peng

  2. Department of Molecular Orthopaedics, Bei**g Institute of Traumatology and Orthopaedics, Bei**g, 100035, China

    Qianqian Wang

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  1. Qi Zhang
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Zhang, Q., Wang, Q., Wang, X. et al. Regorafenib, TAS-102, or fruquintinib for metastatic colorectal cancer: any difference in randomized trials?. Int J Colorectal Dis 35, 295–306 (2020). https://doi.org/10.1007/s00384-019-03477-x

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