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Clinical outcomes of chemotherapy-based therapies for previously treated advanced colorectal cancer: a systematic literature review and meta-analysis

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Abstract

Purpose

The purpose of this study was to evaluate clinical outcomes of standard therapies in previously treated, advanced colorectal cancer (CRC) patients.

Methods

A systematic literature review was conducted in Embase, MEDLINE, and CENTRAL databases (January 2000-July 2021), annual oncology conferences (2019–2021), and clinicaltrials.gov to identify studies evaluating the use of licensed interventions in second-line or later settings. The primary outcome of interest was objective response rate (ORR) and secondary outcomes included progression-free survival (PFS) and overall survival (OS). ORR was pooled using the Freeman-Tukey double arcsine transformation. For survival outcomes, published Kaplan–Meier curves for OS and PFS were digitized to re-construct individual patient-level data and pooled following the methodology described by Combescure et al. (2014).

Results

Twenty-three trials evaluating standard chemotherapies with or without targeted therapies across 4,791 advanced CRC patients contributed to our meta-analysis. In the second-line setting, the random effects pooled estimate of ORR was 22.4% (95% confidence interval (CI): 18.0, 27.1), median PFS was 7.0 months (95% CI: 6.4, 7.4), and median OS was 14.9 months (95% CI: 13.6, 16.1). In the third-line or later setting, the random effects pooled estimate of ORR was 1.7% (95% CI: 0.8, 2.7), median PFS was 2.3 months (95% CI: 2.0, 2.8), and median OS was 8.2 months (95% CI: 7.1, 9.1).

Conclusion

Standard treatments have limited efficacy in the second-line or later setting with worsening outcomes in later lines. Given the global burden of CRC, further research into novel and emerging therapeutic options following treatment failure is needed.

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Acknowledgements

We would like to thank Manasi Thosar (PRECISIONheor) and Asfar Khan (PRECISIONheor) for their contributions to the systematic literature review. Financial support for the research, authorship, and publication of this manuscript was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

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Authors and Affiliations

  1. Merck & Co., Inc, Rahway, NJ, USA

    Mayur M. Amonkar

  2. MSD, Zurich, Switzerland

    Lauren A. Abderhalden & Brian M. Lang

  3. PRECISIONheor, New York, NY, USA

    Andrew M. Frederickson & Ina Zhang

  4. MSD (UK) Limited, London, UK

    Audrone Aksomaityte

  5. MSD, Paris, France

    Pierre Leconte

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Conception and design (all authors); acquisition and collection of data (IZ and AMF); statistical analyses (LA, AA, and BML); interpretation of data (all authors); draft manuscript (IZ and AMF); critical review of manuscript (all authors). All aspects of the systematic literature review (e.g., searches, screening, and data extraction) were conducted by PRECISIONheor. Analytical decisions were made by study investigators. All authors have read and approved the final version of this manuscript.

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Correspondence to Ina Zhang.

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MMA, LAA, AA, BML, and PL are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, the sponsor of this study and manuscript. IZ and AMF are employees of PRECISIONheor, a healthcare research consultancy which has received funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

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Amonkar, M.M., Abderhalden, L.A., Frederickson, A.M. et al. Clinical outcomes of chemotherapy-based therapies for previously treated advanced colorectal cancer: a systematic literature review and meta-analysis. Int J Colorectal Dis 38, 10 (2023). https://doi.org/10.1007/s00384-022-04301-9

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