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Efficacy and Safety of Supportive Care Biosimilars Among Cancer Patients: A Systematic Review and Meta-Analysis

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A Letter to the Editor to this article was published on 09 October 2019

A Letter to the Editor to this article was published on 09 October 2019

A Correction to this article was published on 21 September 2019

This article has been updated

Abstract

Background

Biologics are widely used to manage the side effects of cancer treatment (e.g., epoetin alfa is used to treat chemotherapy-induced anemia [CIA] and granulocyte colony-stimulating factors [G-CSFs] are used to treat chemotherapy-induced neutropenia [CIN]). As several patents for biologics used in cancer treatment have expired, a number of companies have developed supportive care biosimilars (e.g., epoetin alfa biosimilar, filgrastim biosimilar, pegfilgrastim biosimilar).

Objective

The objective of this study was to synthesize current evidence on the efficacy and safety of supportive care biosimilars compared with their reference biologics in oncology.

Methods

We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, ISI Web of Science and several Chinese databases from their inception dates to December 31, 2018 for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of supportive care biosimilars and their reference biologics in oncology. We pooled results separately for RCTs and observational studies, as such studies involve different patient populations and are designed differently. We pooled binary outcomes using risk ratios (RR) with confidence intervals (CIs) and continuous outcomes using weighted mean differences (WMD) with 95% CIs, then conducted subgroup and sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of evidence.

Results

We identified 29 studies that compared biosimilars of G-CSF or epoetin alfa: one RCT and five cohort studies (total N = 2816) of epoetin alfa biosimilars, and 13 RCTs and 10 cohort studies (total N = 23,561) of G-CSF biosimilars. Despite involving different populations, RCTs and observational studies comparing biosimilars and reference biologics indicated similar efficacy and safety results. Overall, there was no statistically significant difference in any efficacy or safety outcomes between any biosimilars and their corresponding original biologics (all p > 0.05). The quality of GRADE evidence of efficacy and safety outcomes was moderate or low. Findings were robust for all prespecified subgroup and sensitivity analyses.

Conclusion

Existing evidence suggests highly comparable efficacy and safety profiles for supportive care biosimilars and their reference biologics in oncology.

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Change history

  • 21 September 2019

    The authors unintentionally included in the meta-analysis both the initial abstract and the final paper of the study by Puertolas et al. [45, 48]. In order to remove this duplication, the following corrections are required.

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Acknowledgments

The authors thank Sengwee Toh, ScD (Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute), for helping conceive of this research topic.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China

    Jichun Yang, Shuqing Yu, Yusong Yan, Yao Chen & Feng Sun

  2. Primary Care Unit, School of Clinical Medicine, University of Cambridge, Cambridgeshire, CB1 8RN, UK

    Zhirong Yang

  3. Department of Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Hongmei Zeng

  4. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Fei Ma

  5. Department of Medical Oncology, Sun Yat-Sen University Cancer Center/State Key Laboratory of Oncology in South China/Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China

    Yanxia Shi

  6. Phase I Clinical Trial Department of Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Yehui Shi

  7. Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA

    Zilu Zhang

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  3. Zhirong Yang
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  4. Yusong Yan
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  8. Yanxia Shi
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  10. Zilu Zhang
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  11. Feng Sun
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Contributions

FS conceived of the study protocol and revised the manuscript. ZRY and JCY drafted the protocol. FS and JCY conducted the literature search. JCY, YC, YSY, and SQY selected the studies. SQY, YC, YSY, and JCY extracted the data. JCY, ZRY, and FS assessed the quality of evidence using the GRADE framework. ZRY and FS verified the data. ZLZ gave opinions on data analysis. HMZ, FM, YXS, and YHS reevaluated the literature and gave clinical opinions on the results of the study. JCY and SQY analyzed the data and wrote the manuscript. All authors contributed to interpreting the results, reviewing the draft, and finalizing the paper.

Corresponding author

Correspondence to Feng Sun.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 71673003).

Conflict of interest

Jichun Yang, Shuqing Yu, Zhirong Yang, Yusong Yan, Yao Chen, Hongmei Zeng, Fei Ma, Yanxia Shi, Yehui Shi, Zilu Zhang, Feng Sun, and Sengwee Toh declare that they have no conflicts of interest that might influence the results of the study.

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Not required.

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Yang, J., Yu, S., Yang, Z. et al. Efficacy and Safety of Supportive Care Biosimilars Among Cancer Patients: A Systematic Review and Meta-Analysis. BioDrugs 33, 373–389 (2019). https://doi.org/10.1007/s40259-019-00356-3

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  • DOI: https://doi.org/10.1007/s40259-019-00356-3

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