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Clinical Study

Circulating biomarkers and outcomes from a randomised phase 2 trial of gemcitabine versus capecitabine-based chemoradiotherapy for pancreatic cancer

Abstract

Background

The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC).

Methods

Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors.

Results

Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76–21.32) months compared to 11.3 (95% CI 9.86–15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04–8.65; p = 0.037).

Conclusions

CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer.

Clinical trial registration

The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).

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Fig. 1

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Author information

Affiliations

Authors

Contributions

C.N.H., E.O.N. and S.M. devised and led the translational component SCALOP trial. FW performed the in vitro measurement of biomarkers. C.M.C., C.S.W-B. and C.N.H. led the analysis of data, with contributions from E.E.P., A.G.A., R.O., A.S., C.M.J., D.L.I.H. and T.M. All authors (F.W., C.M.C., E.E.P., C.S.W-B., A.G.A., R.O., A.S., C.M.J., D.L.I.H., T.M., C.N.H., E.E.O.N., S.M.) contributed to the interpretation of the results. F.W., C.C., C.M.J. and S.M. authored the initial drafts of the paper. All authors have contributed to subsequent redrafting of the paper, and all have approved the final version. All authors agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Somnath Mukherjee.

Ethics declarations

Ethics approval and consent to participate

The trial protocol was approved by the UK Medicines and Healthcare Products Regulatory Agency and a multicentre research ethics committee. Written informed consent was obtained for all patients who participated in SCALOP, as well as for the optional translational sample collection component. The study was performed in accordance with the Declaration of Helsinki.

Consent to publish

No relevant identifiable patient data.

Data availability

Anonymised data available on request from the corresponding author.

Competing interests

The authors declare no competing interests.

Funding information

C.C., C.W.B. and C.N.H. are supported by Cancer Research UK Clinical Trials Unit core funding. C.M.J. is supported by a Wellcome Trust Clinical Research Fellowship. E.O.N. receives funding from the Kidani Memorial Trust and Cancer Research UK. S.M. is supported by funding from the NIHR Oxford Biomedical Research Centre.

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Willenbrock, F., Cox, C.M., Parkes, E.E. et al. Circulating biomarkers and outcomes from a randomised phase 2 trial of gemcitabine versus capecitabine-based chemoradiotherapy for pancreatic cancer. Br J Cancer 124, 581–586 (2021). https://doi.org/10.1038/s41416-020-01120-z

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