Combining tumour response and progression free survival as surrogate endpoints for overall survival in advanced colorectal cancer
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, 101665Version
- VoR (Version of Record)
Published in
Cancer Epidemiology: the international journal of cancer epidemiology, detection and preventionVolume
64Pagination
101665Publisher
Elsevierissn
0361-090XAcceptance date
2019-12-17Copyright date
2020Available date
2020-01-05Publisher DOI
Publisher version
https://www.sciencedirect.com/science/article/pii/S1877782119301754Language
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