University of Leicester
Browse
1-s2.0-S1877782119301754-main.pdf (463.32 kB)

Combining tumour response and progression free survival as surrogate endpoints for overall survival in advanced colorectal cancer

Download (463.32 kB)
Version 2 2020-05-05, 11:31
Version 1 2020-05-05, 11:30
journal contribution
posted on 2020-05-05, 11:31 authored by Eleni Elia, Nicolas Staedler, Oriana Ciani, Rod Taylor, Sylwia Bujkiewicz

Background

Progression free survival (PFS) and tumour response (TR) have been investigated as surrogate endpoints for overall survival (OS) in advanced colorectal cancer (aCRC), however their validity has been shown to be suboptimal. In recent years, meta-analytic methods allowing for use of multiple surrogate endpoints jointly have been proposed. Our aim was to assess if PFS and TR used jointly as surrogate endpoints to OS improve their predictive value.

Methods

Data were obtained from a systematic review of randomised controlled trials investigating effectiveness of pharmacological therapies in aCRC, including systemic chemotherapies, anti-epidermal growth factor receptor therapies and anti-angiogenic agents. Multivariate meta-analysis was used to model the association patterns between treatment effects on the surrogate endpoints (TR, PFS) and the final outcome (OS).

Results

Analysis of 33 trials reporting treatment effects on all three outcomes showed reasonably strong association between treatment effects on PFS and OS, however the association parameters were obtained with a large uncertainty. A weak surrogate relationship was noted between the treatment effects on TR and OS. Modelling the two surrogate endpoints, TR and PFS, jointly as predictors of treatment effect on OS gave no marked improvement to surrogate association patterns. Modest improvement in the precision of the predicted treatment effects on the final outcome was noted in studies investigating anti-angiogenic therapy, however it was likely due to chance.

Conclusion

The joint use of two surrogate endpoints did not lead to marked improvement in the association between treatment effects on surrogate and final endpoints in advanced colorectal cancer.

Funding

This work was supported by the Medical Research Council (MRC) Methodology Research Programme [New Investigator Research Grant MR/L009854/1awarded to Sylwia Bujkiewicz]. Eleni Elia and Sylwia Bujkiewicz were financially supported by this grant while being employed by the University of Leicester. The funder had no involvement in the conduct of this research. The research presented here used the ALICE High Performance Computing Facility at the University of Leicester.

History

Citation

Cancer Epidemiology Volume 64, February 2020, 101665

Version

  • VoR (Version of Record)

Published in

Cancer Epidemiology: the international journal of cancer epidemiology, detection and prevention

Volume

64

Pagination

101665

Publisher

Elsevier

issn

0361-090X

Acceptance date

2019-12-17

Copyright date

2020

Available date

2020-01-05

Publisher version

https://www.sciencedirect.com/science/article/pii/S1877782119301754

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC