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Efficacy and Safety of Anti-cancer Biosimilars Compared to Reference Biologics in Oncology: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Abstract

Background

Many biosimilars of monoclonal antibodies (mAbs) are becoming increasingly available as anticancer therapies, such as the rituximab, bevacizumab, and trastuzumab biosimilars. However, no comprehensive summary of their efficacy and safety is available.

Objective

This study synthesized current evidence on the efficacy and safety of mAb biosimilars relative to their reference biologics among cancer patients.

Methods

We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, the 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 biosimilars with reference biologics used in oncology. The binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs), continuous outcomes using weighted mean difference (WMD) with 95% CIs, and time-to-event outcomes using hazard ratios (HRs). Subgroup and sensitivity analyses were conducted following this. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the evidence.

Results

We did not find any comparative observational studies that fit the criteria. Twenty-three RCTs were identified for biosimilars of three mAbs, of which eight RCTs examined rituximab biosimilars (total N = 1534), six RCTs were for bevacizumab biosimilars (total N = 1897), and nine were for trastuzumab biosimilars (total N = 4953), respectively. The quality of the GRADE evidence for efficacy and safety outcomes was moderate or low. The findings were robust for all pre-specified subgroup and sensitivity analyses.

Conclusion

The existing evidence suggests highly comparable efficacy and safety profiles between mAb biosimilars and their reference biologics in oncological drugs.

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Acknowledgements

The authors thank Sengwee Toh (Associate Professor, ScD, Department of Population Medicine, Harvard Medical School & Harvard Pilgrim Health Care Institute) for helping conceive 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, CB18RN, 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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  1. Jichun Yang
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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 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 performed study selection. 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 an opinion on the data analyses. HMZ, FM, YXS, and YHS re-evaluated the literature and gave clinical opinions on the results of the study. JCY and ZRY analyzed the data and wrote the manuscript. All authors helped interpret the results, reviewed drafts of the paper, and finalized 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 (NSFC, 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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Yang, J., Yu, S., Yang, Z. et al. Efficacy and Safety of Anti-cancer Biosimilars Compared to Reference Biologics in Oncology: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. BioDrugs 33, 357–371 (2019). https://doi.org/10.1007/s40259-019-00358-1

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